Differential effect of free intake versus oral perfusion of sucrose in conditioned taste aversion in rats.

Five experiments were designed to investigate LiCl-induced conditioned taste aversion (CTA) obtained in rats whether after free intake of a sucrose solution (active mode) or after forced administration through an intraoral cannula (passive mode). It was found in Experiment 1 that actively conditioned rats showed a slower extinction rate as revealed by repeated two-bottle tests (active testing) as opposed to passively conditioned ones. As these rats underwent a mode change between conditioning and testing, the differential extinction rate might have arisen from this change inducing a generalization decrement effect or acting as a contextual shift. In Experiment 2, no evidence for any generalization decrement was found. The possibility that the mode of sucrose delivery could have contextual properties in CTA through a "renewal test" after extinction and a latent inhibition experiment was further tested in Experiments 3 and 4. When active testing followed passive extinction, a CTA was afresh obtained in rats actively conditioned in active conditions. Latent inhibition was attenuated in rats preexposed in passive conditions and conditioned in active conditions (i.e., when a shift in the drinking mode occurred between preexposure and conditioning). In Experiment 5, intraoral perfusion was used in both groups. The active subjects had to nose poke for intraoral administration of sucrose. The yoked control passive subjects received simultaneously the same amount of sucrose. The levels of CTA differed also from the actively to the passively conditioned subjects. Results are discussed in terms of free intake activity acting as a contextual modulator of CTA.     

Differential involvement of medial prefrontal cortex and basolateral amygdala extracellular signal-regulated kinase in extinction of conditioned taste aversion is dependent on different intervals of extinction following conditioning

Extinction reflects a decrease in the conditioned response (CR) following non-reinforcement of a conditioned stimulus. Behavioral evidence indicates that extinction involves an inhibitory learning mechanism in which the extinguished CR reappears with presentation of an unconditioned stimulus. However, recent studies on fear conditioning suggest that extinction erases the original conditioning if the time interval between fear acquisition and extinction is short. The present study examined the effects of different intervals between acquisition and extinction of the original memory in conditioned taste aversion (CTA). Male Long-Evans rats acquired CTA by associating a 0.2% sucrose solution with malaise induced by i.p. injection of 4 ml/kg 0.15 M LiCl. Two different time intervals, 5 and 24 h, between CTA acquisition and extinction were used. Five or 24 h after CTA acquisition, extinction trials were performed, in which a bottle containing 20 ml of a 0.2% sucrose solution was provided for 10 min without subsequent LiCl injection. If sucrose consumption during the extinction trials was greater than the average water consumption, then rats were considered to have reached CTA extinction. Rats subjected to extinction trials lasting 24 h, but not 5 h, after acquisition re-exhibited the extinguished CR following injection of 0.15 M LiCl alone 7 days after acquisition. Extracellular signal-regulated kinase (ERK) in the medial prefrontal cortex (mPFC) and basolateral nucleus of the amygdala (BLA) was examined by Western blot after the first extinction trial. ERK activation in the mPFC was induced after the extinction trial beginning 5 h after acquisition, whereas the extinction trial performed 24 h after acquisition induced ERK activation in the BLA. These data suggest that the original conditioning can be inhibited or retained by CTA extinction depending on the time interval between acquisition and extinction and that the ERK transduction pathway in the mPFC and BLA is differentially involved in these processes.     

Experience with activity based anorexia enhances conditioned taste aversion learning in rats

Activity based anorexia (ABA) is a model that mimics the self-starvation and hyperactivity features of anorexia nervosa (AN). This study investigated whether a history of ABA will enhance food avoidance learning and retard its extinction in female rats. We compared the acquisition and extinction of a conditioned taste aversion (CTA) in naive (ad lib with no access to RW), ABA, and pair-fed to the food intake of ABA (with access to a locked RW) female Sprague-Dawley rats. The CTA conditioning was conducted after the ABA and pair-fed rats had recovered to their pre-food restriction body weights. For the CTA learning, 0.3 M sucrose consumption was followed by low doses LiCl (0.009 M or 0.018 M at 1.33 ml/100 g of body weight, IP) injection. The results revealed that the ABA rats acquired an aversion to sucrose significantly sooner than the naive controls. Furthermore, they completely avoided sucrose while the naive and pair-fed controls still sampled it by the end of 10 conditioning trials. When extinction was assessed by 1-bottle and 2-bottle tests, the ABA rats extinguished more slowly than the controls. However, the differences in sucrose aversion extinction between the ABA and control rats were only significant in the 1-bottle test. These data suggest that experience with AN-like behaviors results in an acquired aversion to a preferred food sooner and a longer retention of the negative food associations. These findings have implications for understanding the persistence of aberrant eating behaviors in eating disorders.     

c-Fos Induction in the Rat Nucleus of the Solitary Tract by Intraoral Quinine Infusion Depends on Prior Contingent Pairing of Quinine and Lithium Chloride

Intraoral infusions of sucrose or saccharin induce c-Fos-like immunoreactivity (c-FLI) in the intermediate nucleus of the solitary tract (iNTS) of rats after acquisition of a conditioned taste aversion (CTA). The induction of c-FLI in the iNTS may be a consequence of the shift in behavioral response from ingestive to aversive behaviors that characterize acquisition and expression of a CTA. To test this hypothesis, rats were intraorally infused with 0.3 mM quinine sulfate, an aversive taste, 1. prior to conditioning, 2. after 3 noncontingent (unpaired) infusions of quinine and toxic lithium chloride (LiCl) injections, 3. after conditioning with 3 contingent pairings of quinine and LiCl, and 4. after extinction with repeated unpaired infusions of quinine. Intraoral infusions of quinine induced c-FLI in the iNTS only after acquisition of a CTA against quinine; quinine failed to induce c-FLI in the iNTS of unconditioned, noncontingently treated, or extinguished rats. The pattern of c-FLI in the iNTS induced by expression of a CTA against quinine was quantitatively and anatomically similar to that elicited by sucrose in rats expressing a CTA against sucrose. We conclude that aversive responses per se are not sufficient to induce c-FLI in the iNTS. Furthermore, contingent pairing of quinine and LiCl does not cause a shift in behavioral response from palatable, ingestive behaviors to aversive behaviors as in acquisition of a CTA against sucrose. Thus, we also conclude that a shift in behavior from ingestive to aversive responses is not required for increased c-FLI expression in the iNTS during CTA expression. Therefore, the induction of c-FLI in the iNTS during expression of a CTA may be correlated with neuronal processes specific to acquisition and expression of a CTA.     

The forgetting of stimulus attributes in latent inhibition

Numerous studies have demonstrated that the forgetting of stimulus attributes is a common occurrence; that is, organisms forget the specific characteristics of training stimuli over long retention intervals, while retaining general information of the training stimuli themselves. However, most studies have examined this effect after a learning episode, and there have been virtually no accounts to test whether the forgetting of attributes occurs for stimuli presented prior to training. Therefore, this experiment was designed to test that possibility, and it examined whether the forgetting of stimulus attributes occurred prior to training for the flavor stimulus in a conditioned taste aversion (CTA) procedure. Specifically, a latent inhibition (LI) procedure was used to measure the extent of forgetting for a pre-exposed flavor over short and long retention intervals. The results indicate that rats forgot the specific characteristics of the flavor stimulus (CS) while retaining memory for pre-exposure sessions over a long retention interval. That is, subjects pre-exposed and conditioned with different concentrations of sucrose showed no LI effect with a 1-day delay between pre-exposure and training, but demonstrated a generalized LI with an 8-day delay between pre-exposure and conditioning. This experiment provides further evidence for the robustness of the forgetting of stimulus attributes, and demonstrates that this specific type of forgetting also occurs prior to the learning of a CTA task.     

Conditioned taste aversion in lean and obese rats with ventromedial hypothalamic knife cuts

The development of a conditioned taste aversion (CTA) was assessed in rats made hyperphagic with parasagittal knife cuts in the ventromedial hypothalamus (VMH). The animals were water deprived and presented with a .1% saccharin solution paired with injections of either lithium chloride or sodium chloride. In Experiment 1, VMH rats tested at a nonobese weight level did not differ from sham-operated control rats in the acquisition and extinction of the CTA. In Experiment 2, moderately obese VMH rats displayed a stronger CTA than did sham-operated control rats as evidenced by a slower rate of extinction. This effect was not due to the higher absolute dose of LiCl given to the obese VMH rats. A second group of obese VMH rats given an amount of LiCl equivalent to that given to the control rats also displayed retarded extinction of the CTA. The results of these experiments demonstrate that hyperphagia-inducing knife cuts do not alter aversive taste conditioning in rats but that hypothalamic obesity does enhance conditioned taste aversions. This may reflect an obesity-induced suppression in appetitive motivation.     

Conditioned taste aversion in vasopressin-deficient rats (Brattleboro strain)

Brattleboro rats are homozygous for diabetes insipidus (DI), lacking the ability to synthesize vasopressin. Previous studies reported learning deficits in DI rats on passive avoidance tasks using footshock. Other studies, however, could not replicate these results. In two experiments, we studied the learning of DI and control Long Evans (LE) rats in a different avoidance paradigm: conditioned taste aversion (CTA). In the first experiment a mild CTA to saccharin was established gradually using low levels of an illness-inducing agent (lithium chloride). In the second experiment a strong CTA was established in one acquisition trial and the extinction of the conditioned aversion was followed for 12 trials. The two experiments found no differences between the DI and LE rats in either the magnitude or the rate of acquisition and extinction of the CTA. These results suggest that vasopressin is not involved in the acquisition and retention of CTA, and support previous studies indicating that vasopressin may not be involved in avoidance learning.     

Taste reactivity as a dependent measure of the rapid formation of conditioned taste aversion: a tool for the neural analysis of taste-visceral associations

Several explanations may account for deficits in the ability of animals to form taste aversions following neural manipulations. These encompass impairments in conditioned stimulus (CS) and unconditioned stimulus (US) processing, conditioned response (CR) measurement, and expression, memory, and taste-visceral integration. A behavioral procedure that aids in the distinction between some of these possibilities is presented. In Experiment 1, 10 rats received seven intraoral (IO) infusions of sucrose (30 s, 0.55 ml) spaced every 5 min starting immediately after the injection of 3.0 mEq/kg of lithium chloride (LiCl). Control rats (n = 12) were treated identically except that they were injected with sodium chloride (NaCl). Oromotor and somatic taste reactivity behaviors were videotaped and analyzed. Lithium-injected rats systematically decreased their ingestive taste reactivity behavior over time, whereas aversive behavior increased. Control rats maintained high and stable levels of ingestive responding and demonstrated virtually no aversive behavior over the 30-min period following sodium injection. Rats were tested several days later for the presence of a conditioned taste aversion (CTA). Rats previously injected with lithium during sucrose infusions demonstrated significantly more aversive behavior than the control group, which demonstrated none. There were no differences in the level of ingestive behavior displayed by the two groups on the CTA test. Experiment 3 revealed that when similarly treated rats were tested for a CTA while in a lithium-induced state, a difference in the ingestive behavior between the two groups was observed. In Experiment 2, naive rats were injected with either NaCl or LiCl but did not receive their first sucrose infusion until 20 min later. These rats also received sucrose infusions at 25 and 30 min postinjection. There were no differences in the taste reactivity behavior displayed by lithium- or sodium-injected rats during any of the sucrose infusions. Collectively, these findings indicate that rats dramatically change their oromotor responses to sucrose during the period following LiCl administration, provided that the infusions start immediately after injection. Furthermore, this time-related behavioral change is predominantly attributable to associative processes. This paradigm can be useful in distinguishing between neural manipulations that affect the establishment of taste-visceral associations from others that affect the animal's ability to retain such associations over the commonly employed 24-hr conditioning-test interval.     

Acute, but not chronic, exposure to d-cycloserine facilitates extinction and modulates spontaneous recovery of a conditioned taste aversion

D-cycloserine, the glutamate N-methyl-D-aspartate receptor partial agonist, has been reported to facilitate the extinction of learned fears acquired in both naturalistic and laboratory settings. The current study extended this literature by evaluating the ability of either chronic or acute administrations of DCS to modulate the extinction and spontaneous recovery of a conditioned taste aversion (CTA). Twenty-three hour fluid-deprived Sprague-Dawley rats acquired a strong CTA following 3 pairings of a conditioned stimulus (CS; 0.3% oral saccharin)+unconditioned stimulus [US; 81 mg/kg (i.p.) lithium chloride (LiCl)]. In separate groups of rats, we then employed 2 different extinction paradigms: (1) CS-only (CSO-EXT) in which saccharin was presented every-other day, or (2) Explicitly Unpaired (EU-EXT) in which both saccharin and LiCl were presented but on alternate days. Previous studies have indicated that the EU-EXT procedure speeds up the extinction process. Further, spontaneous recovery of a CTA emerges following CSO-EXT but the EU-EXT paradigm causes a suppression of spontaneous recovery. DCS (15 mg/kg, i.p.) was administered immediately after daily liquid presentations (saccharin or water, alternate days) during the extinction period. In an acute drug manipulation, DCS (15 mg/kg, i.p.) or saline control injections were administered for 4 days only. This was done during one of 3 different phases of extinction [i.e., static (2-5%), early dynamic (8-16%), or middle dynamic (20-40%) saccharin reacceptance]. Other animals assigned to the chronic DCS condition received daily DCS (15 mg/kg, i.p.) throughout extinction. Changes in saccharin drinking in these animals were compared to the data from rats that received no drug (saline controls). Once rats met our criterion for asymptotic extinction (90% reacceptance of the CS) they entered a 30-day latency period during which they received water for 1 h/day. The day after the completion of the latency period, a final opportunity to drink saccharin was provided (spontaneous recovery test). Saline-treated control rats that went through the EU-EXT procedure achieved asymptotic extinction more quickly than did the CSO-EXT rats and did not exhibit a spontaneous recovery of the CTA. Chronic DCS treatments did not significantly reduce the time to achieve asymptotic CTA extinction in rats exposed to either CSO or EU extinction methods. Further, animals treated with DCS throughout EU-EXT exhibited a spontaneous recovery of the CTA whereas the saline-treated, EU-EXT rats did not. Thus, chronic DCS treatment did not shorten the time to extinguish a CTA and this treatment eliminated the ability of EU-EXT to block spontaneous recovery of the CTA. Acute DCS treatments were more effective in reducing the time required to extinguish a CTA than were chronic drug treatments. Moreover, the timing of these acute DCS treatments affected spontaneous recovery of the CTA depending on the extinction method employed. Acute DCS administrations later in extinction were more effective in reducing spontaneous recovery than were early administrations if the rats went through the CSO-EXT procedure. However, late-in-extinction administrations of DCS facilitated spontaneous recovery of the CTA in rats that experienced the EU-EXT method. These data agree with other findings suggesting that DCS treatments are more effective when administered a limited number of times. Our data extend these findings to the CTA paradigm and further suggest that, depending on the extinction paradigm employed, acute exposure to DCS can speed up CTA extinction and reduce spontaneous recovery of the aversion. The timing of the acute DCS treatment during extinction is generally less important than its duration in predicting the rate of CTA extinction. However, the timing of acute DCS treatments during extinction and the method of extinction employed can interact to affect spontaneous recovery of a CTA.     

Effect of conditioning method and testing method on strength of lithium-induced taste aversion learning

Here the authors evaluated the effect of the method of conditioning (bottle or intraoral [IO] infusion) on the strength of a flavor-drug association when measured in a standard 1-bottle consumption test or when measured by IO infusion in a taste reactivity test. When tested with the bottle test in Experiment 1, rats conditioned by bottle displayed stronger taste avoidance than those conditioned by IO infusion. When tested for rejection reactions with the taste reactivity test in Experiment 2, rats conditioned by infusion displayed a stronger aversion than did rats conditioned by bottle. The results suggest that when the contextual cues of conditioning are similar at conditioning and testing, a stronger association is evident regardless of the individual specifics of each method. These results may shed light on recent reports that different neural mechanisms are involved in conditioning by active consumption and passive infusion.     

Cycloheximide impairs reconsolidation of a contextually reactivated memory in a conditioned taste aversion paradigm

Rats were used to examine the impact of systemic protein synthesis inhibition (PSI) on the reconsolidation of a contextually reactivated memory of conditioned taste aversion (CTA). Rats were administered intraperitoneal injections of saline or lithium chloride (LiCl; .15 M) following exposure to a novel sucrose solution in a unique context. Seven days later, rats were injected subcutaneously with saline or cycloheximide (CXM; 1 mg/kg) and returned to their home cage or placed into the CTA training context in the absence of the target conditioned stimulus to reactivate the training memory. At testing, LiCl-trained rats that had been given CXM at reactivation had significantly greater difference scores (sucrose-water) in comparison with LiCl/CXM rats that had not been given a reactivation treatment and LiCl/saline memory-reactivated rats. These results suggest that context re-exposure effectively reactivates memory of CTA training that may be weakened through PSI. Extinction tests revealed rapid attenuation of taste aversions in all of the LiCl-injected groups. The involvement of taste-potentiated aversions and the role of the context in taste aversion conditioning are discussed.     

Assessing the role of inferior olivary sensory signaling in the expression of conditioned eyeblinks using a combined glutamate/GABAA receptor antagonist protocol

The inferior olive (IO) is a major component of the eyeblink conditioning neural network. The cerebellar learning hypothesis assumes that the IO supplies the cerebellum with a "teaching" unconditioned stimulus input required for the acquisition of the conditioned response (CR) and predicts that inactivating this input leads to the extinction of CRs. Previous tests of this prediction attempted to block the teaching input by blocking glutamatergic sensory inputs in the IO. These tests were inconclusive because blocking glutamate neurotransmission in the IO produces a nonspecific tonic malfunction of cerebellar circuits. The purpose of the present experiment was to examine whether the behavioral outcomes of blocking glutamate receptors in the IO could be counterbalanced by reducing GABA-mediated inhibition in the IO. We found that injecting the IO with the glutamate antagonist γ-d-glutamylglycine (DGG) abolished previously learned CRs, whereas injecting the GABA(A) receptor antagonist gabazine at the same site did not affect CR incidence but shortened CR latencies and produced tonic eyelid closure. To test whether the glutamate antagonist-induced behavioral deficit could be offset by elevating IO activity with GABA(A) antagonists, rabbits were first injected with DGG and then with gabazine in the same training session. While DGG abolished CRs, follow-up injections of gabazine accelerated their recovery. These findings suggest that the level of IO neuronal activity is critical for the performance of CRs, and that combined pharmacological approaches that maintain spontaneous activity at near normal levels hold tremendous potential for unveiling the role of IO-mediated signals in eyeblink conditioning.     

Cortical substrates of taste aversion learning: involvement of dorsolateral amygdaloid nuclei and temporal neocortex in taste aversion learning

The amygdaloid complex is functionally implicated in conditioned taste aversion (CTA) learning. Results of previous neurobehavioral studies have provided equivocal evidence concerning the involvement of specific amygdaloid nuclei in CTA learning. The present study was conducted to examine the involvement of the central (CE), lateral (LA), and basolateral (BL) amygdaloid nuclei and the temporal neocortices (area 20) in CTA learning. To that end, distinct groups of rats received bilateral electrolytic lesion placements in the CE, LA, BL, or the temporal neocortices. Control animals received scalp and meningeal incisions only. Following recovery, animals were habituated to a restricted drinking schedule with distilled water. Animals then received CTA conditioning, with LiCl used both as the conditioned stimulus and as the unconditioned stimulus. Anterograde degeneration histologies were performed on all brain tissue to evaluate relations between CTA learning deficits and axonal pathology induced by lesion placements. Results of behavioral manipulations indicated that destruction of the CE, LA, or temporal neocortex impaired CTA acquisition, but damage induced to the basolateral amygdaloid nucleus did not. Anatomical observations indicated that degeneration of amygdalofugal and/or corticofugal projections to the convolutions of the olfactory tubercle (medial), subthalamic nucleus, and the parabrachial complex is correlated with CTA learning deficits. These results indicate that destruction of the dorsolateral amygdaloid nuclei and/or the temporal neocortices may produce CTA learning deficits by affecting olfactory, gustatory, and/or gastrointestinal processing in various portions of the forebrain.     

Water-deprivation prevents morphine-, but not LiCl-induced, suppression of sucrose intake.

Intake of a saccharin-conditioned stimulus (CS) can be suppressed following pairing with an aversive agent such as lithium chloride (LiCl) or x-rays (referred to as a conditioned taste aversion or CTA), a highly rewarding sucrose solution (referred to as an anticipatory contrast effect), or a drug of abuse such as morphine or cocaine. Although the suppressive effects of LiCl and sucrose are clear examples of aversive and appetitive conditioning, respectively, it is not certain which properties (aversive or appetitive) mediate the suppressive effects of drugs of abuse. It is known, however, that the suppressive effects of a rewarding sucrose US are attenuated when using a caloric sucrose CS in food deprived rats, while LiCl induced CTAs are much less effected. Standard CTA testing typically is conducted in water-deprived rather than food-deprived rats and, although LiCl is known to suppress intake of a sucrose CS in water-deprived rats, the suppressive effects of drugs of abuse have not been evaluated under these conditions. The present experiment, then, compared the suppressive effects of a standard dose of morphine (15 mg/kg) and a matched dose of LiCl (0.009 M) on intake of a sucrose CS in water-deprived and free-feeding rats. The results showed that both drugs suppressed intake in free-feeding subjects, but only the aversive agent, LiCl, reduced CS intake in the water-deprived rats. This finding dissociates the suppressive effects of morphine and LiCl and, in so doing, aligns the suppressive effects of morphine with those of an appetitive sucrose US.     

Involvement of the anterior insular gustatory neocortex in taste-potentiated odor aversion learning

When an odor conditioned stimulus (CS) precedes illness (unconditioned stimulus; UCS), rats acquire relatively weak odor aversions. Conversely, when a compound odor-taste (flavor) CS precedes illness, rats acquire robust aversions both to the odor and to the taste components of a compound flavor CS. Thus, tastes potentiate odor-illness aversions during toxiphobic conditioning. Such conditioning effects have been referred to as taste-potentiated odor aversion learning (POA). Previous neurobehavioral experiments have shown that the anterior insular gustatory neocortex contributes to conditioned taste aversion (CTA) learning. The present experiment examined the involvement of the anterior insular gustatory neocortex in CTA learning and POA learning. To that end, four distinct groups of rats received bilateral electrolytic lesion placements in the orbitofrontal neocortex, the "somatic" gustatory neocortex, the anterior insular gustatory neocortex or the posterior insular neocortex. Control animals received anesthesia only. Subgroups of animals thereafter received aversion conditioning using either an odor (almond) CS or a compound odor-taste (almond-saccharin) CS. Aversions to the almond odorant and/or saccharin tastant were evaluated during extinction. Results indicated that animals lacking orbitofrontal neocortex or posterior insular neocortex acquired normal CTAs and POAs. Animals lacking somatic gustatory neocortex exhibited impaired CTA learning, yet those animals showed normal POA learning. Lesions centered in the anterior insular neocortex impaired both CTA learning and POA learning. These results demonstrate that the insular gustatory neocortex is uniquely involved in the higher-order integration of odors, tastes and illness.     

On the resistance to extinction of fear conditioned to angry faces

The present study investigated whether, like fear conditioned to pictures of snakes and spiders, fear conditioned to angry faces resists extinction even after verbal instruction and removal of the shock electrode. Participants were trained in a differential Pavlovian fear conditioning procedure with angry face or happy face conditional stimuli (CSs). Prior to extinction, half the participants in each group were informed that no more unconditional stimuli would be presented and the shock electrode was removed. In the absence of this manipulation, participants showed resistance to extinction after training with angry face CSs, but not after training with happy face CSs. Instructed extinction and electrode removal abolished fear conditioning regardless of the emotion expressed by the CS faces. This finding suggests that fear conditioned to angry faces, like fear conditioned to racial out-group faces, is more malleable than fear conditioned to snakes and spiders.     

Effects of central and basolateral amygdala lesions on conditioned taste aversion and latent inhibition

The present study examined the effects of neurotoxic lesions of the central nucleus (CNA) and basolateral complex (BLA) of the amygdala on conditioned taste aversion (CTA) in a latent inhibition design. In Experiment 1, lesions of the CNA were found to have no affect on CTA acquisition regardless of whether the taste conditioned stimulus (CS) was novel or familiar. Lesions of the BLA, although having no influence on performance when the CS was familiar, retarded CTA acquisition when the CS was novel in Experiment 2. The pattern of results suggests that the CTA deficit in rats with BLA lesions may be a secondary consequence of a disruption of perceived stimulus novelty.     

The effect of androgen on the retention of extinction memory after conditioned taste aversion in mice

Conditioned taste aversion (CTA) induced by the application of a novel taste such as sodium saccharin (Sac) as the conditioned stimulus (CS) and a malaise-inducing agent as the unconditioned stimulus (US), results in acquisition of CTA memory to Sac. In contrast, CTA is extinguished by repeated presentations of the CS without the US, resulting in acquisition of the extinction memory. We examined the effects of androgenic hormones on acquisition and retention of extinction memory in mice. We gonadectomized sexually immature mice and continuously administered androgens to these animals. After sexual maturation, the mice underwent a conditioning period followed by an extinction period. Retrieval tests revealed that the androgen-treated group showed significantly greater retention of extinction memory than the non-treated group 5 weeks later, whereas such significant difference was not observed in acquisition of extinction memory. These results demonstrate the enhancing effect of androgens on retention of extinction memory.     

Latent Inhibition and Conditioning in Rat Strains Which Show Differential Prepulse Inhibition

Latent inhibition (LI) is the retardation of associative conditioning resulting from preexposure of the conditioned stimulus (CS) alone prior to conditioning. Schizophrenic patients show deficient prepulse inhibition (PPI) and, at least acutely, deficient LI as well. We recently found that Brown Norway (BN) rats show a PPI deficit compared to Wistar-Kyoto (WKY) rats. If PPI and LI depend on neural processes with common genetic substrates, then LI should be deficient in BN rats as well. Here, LI of a conditioned taste aversion was examined in BN and WKY rats. One group from each strain was preexposed to a saccharin-flavored solution (CS) the day prior to conditioning. For taste aversion conditioning, these two groups again consumed saccharin and were injected with lithium chloride (unconditioned stimulus) 10 min later. A second group from each strain was not preexposed to the CS and was treated identically during conditioning, while a third group was not conditioned (injected with sodium chloride). To test for taste aversion conditioning, saccharin was offered for 20 min/day for 3 days. Nonconditioned BN and WKY rats consumed equal amounts of saccharin on test days. In both strains, conditioned rats showed a saccharin aversion. However, conditioning was less robust in BN than in WKY rats. WKY rats showed good LI of the conditioned taste aversion in that preexposed WKY rats consumed significantly more saccharin on test days than conditioned, nonpreexposed WKY rats. Preexposed BN rats did not consume significantly more saccharin on test days than conditioned, nonpreexposed BN rats. The previously reported deficiency in PPI in the BN rats was confirmed here 1 week after the taste aversion experiment. These results suggest that BN rats show deficient LI as well as PPI and display poor associative learning, a trait also reported in schizophrenia.     

Involvement of the supramammillary nucleus in aversive conditioning

Mechanisms for the retention and retrieval of conditioned taste aversions (CTAs) have yet to be fully defined. The authors explored relevant subcortical forebrain regions by tracking the expression of immediate early genes, c-fos and zif268. The supramammillary nucleus (SuM) was activated following both viscerally based CTA and somatically based inhibitory avoidance (IA). Excitotoxic lesions of the SuM before conditioning caused no disruption of acquisition but accelerated the extinction of both the CTA and IA. In contrast, lesions after CTA conditioning did not impair retention or retrieval. The present study indicates that the SuM is activated by memory-elicited discomfort during retrieval, suggesting that it plays a role in resisting the extinction of a long-term aversive memory.