Conditioned taste aversion: a database

The present commentary describes the availability of a database on conditioned taste aversion learning, the avoidance of fluids and foods previously associated with the aversive effects of a variety of drugs. The database includes articles as early as 1955 by Garcia and his colleagues [Science 122 (1955) 127] (reporting such avoidance in rats) and papers just published given that the database is ongoing and constantly updated. At the printing of this announcement, approximately 2600 papers are included in the database. The database allows the user to search for articles by author(s), key word(s), date, title and journal. These terms can be used as single entries or multiple combinations. Finally, the full database can be viewed by performing the search function without entering any terms in the query window. The database can be accessed at http://www.CTALearning.com.     

Conditioned taste aversion and conditioned drinking: Two independent and opposing effects of 5-hydroxytryptophan?

Four experiments were carried out to examine the effects of 5-HTP in a conditioned taste aversion (CTA) paradigm. Using two-choice tests to measure the CTA, administration of 5-HTP following consumption of a novel flavour caused aversions to saline and saccharin solutions. In single-choice tests 5-HTP reduced consumption of saccharin, sugar cubes and beef-flavoured stock cubes, but only reduced saline consumption if animals had been pretreated with the 5-HTP decarboxylase inhibitor benserazide or the 5-HT receptor antagonist xylamidine, both of which act peripherally. Benserazide did not attenuate the CTA in any experiment. The results are interpreted in terms of two competing behavioural effects of 5-HTP: a centrally-mediated CTA and a peripherally-mediated conditioned drinking response.     

Conditioned taste aversion and cholinergic drugs: pharmacological antagonism

The effectiveness of drugs as unconditioned stimuli (UCSs) in the conditioned taste aversion (CTA) procedure may be influenced by specific pharmacological antagonism. The present studies examined the UCS effects of two carbamates, physostigmine salicylate (PS) and pyridostigmine bromide (PB), and three anticholinergic compounds, atropine methyl nitrate (AMN), atropine sulfate (AS), and benactyzine hydrochloride (BH). Individual drugs, as well as combinations of the carbamates and the anticholinergics, were studied in a two-bottle procedure in rats. The lowest effective doses for eliciting significant CTAs were PS, 0.32 mg/kg; PB, 1.00 mg/kg; AMN, 0.04 mg/kg; AS, 0.07 mg/kg and BH, 0.90 mg/kg, IP. Combinations of PS with either AMN or BH were mutually antagonistic as UCSs, whereas PS with AS was not. PB with AMN, but not with AS, also showed antagonism in the procedure. The present results suggest that the CTA procedure is well-suited for direct examination of cholinergic drug effects and may also be used to explore interactions of different classes of cholinergic drugs.     

Rat strain differences in ethanol self-administration and taste aversion learning

Taste aversion learning was investigated in two inbred strains of rats known to differ in amount of ethanol (EtOH) they will self-administer orally. The "low EtOH preference" strain, WKYs, acquired an aversion to an EtOH solution during self-administration; but a "high preference" strain, M520s, did not. It was shown that a lower dose of EtOH will condition saccharin aversion in WKYs than in M520s, suggesting EtOH is a more effective US in the low preference strain. Analysis of patterns of EtOH self-administration indicates the pattern of the low preference strain is more likely to result in taste aversion learning. The implications of these results for the presumed relation between EtOH preference and other EtOH-related phenotypes is discussed.     

Conditioned taste aversion induced by tryptamine: a temporal analysis

The effects of tryptamine on the induction of a conditioned taste aversion (CTA) to a novel saccharin solution were examined. In a single bottle-repeated injection paradigm, tryptamine (40, 60 and 80 mg/kg, IP) induced a significant CTA. This effect was relatively weak, with only the highest dose tested inducing a progressive decline in saccharin intake across trials. The weak action of tryptamine (40 and 60 mg/kg) was confirmed in a more sensitive CTA paradigm which measured the relative preference for saccharin and water. Results of this experiment also showed that prolonging the duration of action of tryptamine failed to enhance the formation of a CTA. This finding extends previous reports that prolonging the duration of action of a compound does not increase potency in the CTA paradigm, and thus casts doubt on the generality of the duration of action hypothesis.     

Conditioned taste aversion to ethanol induced by zimeldine

Conditioned taste aversions (CTA) were induced to both ethanol and saccharin solutions with the serotonin uptake inhibitor Zimeldine. When animals were pretreated with Zimeldine prior to the presentation of a novel flavour a CTA did not result. However, there is evidence that Zimeldine induces an unconditioned suppression of drinking. These results are discussed in terms of their relevance to Zimeldine's effects on voluntary ethanol consumption.     

Conditioned taste aversion and place preference with buspirone and gepirone

The effects of the nonbenzodiazepine anxiolytics buspirone and gepirone were compared to diazepam at 1, 3, and 10 mg/kg using the conditioned taste aversion (CTA) paradigm. Buspirone and gepirone produced stronger CTA than diazepam (3 and 10 mg/kg) across repeated conditioning trials, indicating that these nonbenzodiazepine anxiolytics may have stronger aversive properties than diazepam. The effects of buspirone and gepirone (1 and 3 mg/kg) were also assessed using the conditioned place preference (CPP) paradigm. Both buspirone (1 and 3 mg/kg) and gepirone (3 mg/kg only) produced CPP, indicating that these drugs may have rewarding properties, and that buspirone is more potent than gepirone in producing CPP. These findings demonstrate that buspirone and gepirone have affective properties similar to abused drugs, and may therefore have abuse potential. It was also demonstrated that buspirone (3 mg/kg), but not gepirone (3 mg/kg), increased dopamine (DA) synthesis in the nucleus accumbens, a mesolimbic brain area thought to be involved in drug reward.     

Conditioned taste aversion as an index of lead toxicity

Rats treated with lead acetate following the consumption of a solution with a distinct taste exhibited an aversion to the initially consumed solution. Conditioned taste aversion was reliably induced with 10–20 mg/kg lead acetate. Repeated treatment with lead did not enhance this effect when measured either in forrced or in free choice conditions. The utility of the taste aversion procedure for evaluation of toxic agents is discussed.     

Conditioned taste aversion induced by organophosphate compounds in rats

Three organophosphate compounds, dichlorvos, parathion and diisopropylfluorophosphate were tested as an unconditioned stimulus in the conditioned taste aversion (CTA) test. All organophosphates caused a dose-dependent CTA in rats at doses which did not induce any other signs of toxicity. Experiments with dichlorvos showed that the minimum dose which caused CTA did not alter the rats' sensitivity to pain or their behavior in either an open field or an inclined plane. Cholinesterase activity was inhibited in a dose-dependent manner in brain and plasma after administration of the organophosphates and CTA was correlated with the degree of plasma cholinesterase inhibition. CTA appears to be a sensitive indicator of neurobehavioral effects of mild exposure to organophosphates which causes only 30-40% inhibition of plasma cholinesterase.     

Conditioned taste aversion: modulation by 5-HT receptor activity and corticosterone

Two experiments were designed to elucidate the involvement of the hypothalamic-pituitary-adrenal axis and the 5-hydroxytryptamine (5-HT) system in the acquisition of lithium chloride-conditioned taste aversion. In Experiment 1, rats were administered either vehicle or 50 mg/kg nefazodone daily for 4 weeks. Rats were treated with 22 mg/kg of lithium chloride in order to produce conditioned taste aversion to a sucrose solution. Three days later, nefazodone completely blocked the lithium chloride-conditioned taste aversion. In Experiment 2, the effects of chronic corticosterone administration on lithium chloride-conditioned taste aversion were investigated. Twenty male rats received either corticosterone at a dose of (50 mg/kg) or vehicle injections over a period of 14 consecutive days. Lithium chloride-conditioned taste aversion was potentiated in rats treated with corticosterone. Additionally, corticosterone-treated animals required more trials to reach extinction. These results suggest the involvement of both the 5-HT system and the hypothalamic-pituitary-adrenal axis in lithium chloride-conditioned taste aversion.     

Conditioned taste aversion to chlorpromazine,but not to haloperidol

Using in rats a Conditioned Taste Aversion (CTA) procedure, chlorpromazine was shown to possess significant US properties at the highest dose tested (8 mg/kg IP repeated four times). In contrast, haloperidol failed to exert a similar effect at a dosage (1.6 mg/kg IP X 4) at least twice as high, in terms of pharmacological activity, as the effective chlorpromazine dosage. These data suggest that the induction of neuroleptic extrapyramidal side effects and the antidopaminergic properties shared by the two drugs may not be responsible for the aversive effect of chlorpromazine. However, it cannot be excluded than haloperidol produces an aversion which is antagonized by some action of the drug not shared by chlorpromazine.     

Control of polydipsic drinking by a taste aversion procedure

Rats were given daily sessions with free access to food and saccharin flavored water. After fluid consumption had stabilized food was delivered once every minute. Water was always available in the home cage. All rats showed the marked increase in fluid consumption known as schedule-induced polydipsia. The rats were then poisoned with lithium chloride after each of three sessions in an attempt to condition a taste aversion to the saccharin. On recovery from the toxicosis all rats showed first a reduction and then a recovery in saccharin intake. To establish the nature of this effect, the rats were poisoned after saccharin consumption in the home cage. Again there was a marked reduction in polydipsic drinking in the experimental chamber. These results indicate that common incentive mechanisms govern normal and polydipsic drinking and stand in contrast to published results pointing to different drive systems in the brain mediating normal and polydipsic drinking.     

Conditioned taste aversion induced by inhalation exposure to methyl bromide in rats

The toxic effect of methyl bromide vapor was assessed by a conditioned taste aversion regime. Rats kept under a water deprivation schedule for 7 days, were permitted access to 0.3% (w/v) sodium saccharin, and were exposed to methyl bromide at 0, 25, 50, and 100 ppm for 4 h. 3 days after the exposure, saccharin preference tests were carried out, revealing dose-dependent saccharin aversion in the exposure group. This result suggests that the conditioned taste aversion method is effective for assessing the toxicity of gaseous substances such as methyl bromide.     

Protective behavioral strategies mediate the effect of drinking motives on alcohol use among heavy drinking college students: gender and race differences

Objective

This study examined the extent to which protective behavioral strategies (PBS) mediated the influence of drinking motives on alcohol consumption, and if these hypothesized relationships were corroborated across subsamples of gender and race.

Method

Online surveys were completed by 1592 heavy drinking college undergraduates from two universities (49.9% male and 50.1% female; 76.9% Caucasian and 23.1% Asian). Independent samples t-tests compared males and females as well as Caucasians and Asians on measures of drinking motives, PBS use, and alcohol consumption, and structural equation models examined the mediating role of PBS.

Results

Consistent with predictions, t-tests revealed that males reported greater levels of consumption than females, but females reported greater use of PBS than males. Caucasians reported greater consumption levels, endorsed higher enhancement motives, and higher PBS related to serious harm reduction, but Asians endorsed higher coping and conformity motives, and PBS focused on stopping/limiting drinking. In multiple-sample SEM analyses, PBS were shown to largely mediate the relationship between motives and consumption in all demographic subsamples.

Conclusions

Findings indicate that PBS use leads to reductions in drinking despite pre-established drinking motives, hence pointing to the potential value of standalone PBS skills training interventions in lowering alcohol use among diverse groups of heavy drinking college students.     

Genetic differences in naloxone enhancement of ethanol-induced conditioned taste aversion

The influence of the opioid system on acquisition of an ethanol-induced conditioned taste aversion was examined in alcohol-preferring and avoiding inbred strains of mice (C57BL/6J and DBA/2J). Fluid-deprived mice from each strain received either ethanol alone, naloxone alone, or both ethanol and naloxone immediately after access to a novel tasting fluid. Naloxone alone (1 or 3 mg/kg) did not induce a conditioned taste aversion in either strain of mice. Administration of ethanol (1.5 g/kg) to DBA/2J mice produced a moderate taste aversion that was not affected by co-administration of naloxone. Although ethanol administered alone (3 g/kg) did not cause a taste aversion in C57BL/6J mice, the combination of ethanol and the higher dose of naloxone produced a significant taste aversion that increased across trials. A second experiment addressed the possibility that naloxone failed to enhance the ethanol-induced condition taste aversion in DBA/2J mice due to a floor effect on consumption. A lower ethanol dose (1 g/kg) was given alone or in combination with naloxone (1 or 3 mg/kg). Again, ethanol produced a moderate conditioned taste aversion that was not potentiated by naloxone. Subsequent conditioning with a high ethanol dose produced further suppression of intake, confirming that naloxone's failure to enhance aversion on earlier trials was not due to a floor effect. These data demonstrate a strain specific interaction between the aversive effect of ethanol and naloxone. More specifically, the results indicate that blockade of opioid receptors enhances the aversive effect of ethanol in C57BL/6J but not DBA/2J mice, suggesting that genetically determined differences in the endogenous opioid system of alcohol-preferring mice may mitigate ethanol's aversive effect.     

Strain differences in the acquisition of nicotine-induced conditioned taste aversion

Lewis (LEW) and Fischer (F344) rat strains differ on a variety of physiological and behavioral endpoints, including reactivity to drugs of abuse. Although they differ in drug reactivity, such assessments are generally limited to morphine and cocaine. To determine if these differences generalize to other drugs, the present study examined these strains for their reactivity to the affective properties of nicotine, specifically their sensitivity to nicotine in the conditioned taste aversion preparation. For four or five conditioning cycles given every other day, rats from both strains were allowed access to saccharin and injected with nicotine (0.1, 0.4, 0.8 mg/kg) or vehicle. On intervening days, all rats were given access to water and injected with vehicle. Under this one-bottle training and testing procedure, neither strain displayed aversions at the lowest dose of nicotine (0.1 mg/kg). Aversions were evident for both strains at 0.4 and 0.8 mg/kg, although the F344 rats acquired the aversions at 0.4 mg/kg faster and displayed a significantly greater aversion at 0.8 mg/kg than subjects from the LEW strain. For both strains, aversions were evident at all doses (and in a dose-dependent manner) when subjects were given access to saccharin and water in a two-bottle test. There were, however, no strain differences on this test. Differences between the two strains in their acquisition of nicotine-induced taste aversions were discussed in the context of aversion assessments with other compounds as well as in relation to differences in the self-administration of nicotine in the two strains.     

Conditioned saccharin taste aversion induced by mycotoxins in rats: lack of effect of ochratoxin A

The present study examined the putative aversive action of ochratoxin A (OA) using a conditioned saccharin aversion paradigm. Adult male rats consumed a 0.1% saccharin solution then were treated (IP) with either a 5% NaHCO3 vehicle (negative control), 32 mg/kg LiCl (positive control) or 0.75, 1.5 or 3.0 mg/kg OA. Twenty-four hours later, the rats were given a choice between tap water and the 0.1% saccharin solution. Rats treated with the vehicle or any of the doses of OA exhibited a marked preference for the saccharin solution, whereas the rats treated with LiCl exhibited a marked rejection of the saccharin solution. The implications of these data for an understanding of mycotoxicosis are discussed.     

The effects of cocaine, alcohol and cocaine/alcohol combinations in conditioned taste aversion learning

We have recently reported that alcohol attenuates cocaine place preferences. Although the basis for this effect is unknown, alcohol may attenuate cocaine reward by potentiating its aversive effects. To examine this possibility, these experiments assessed the effects of alcohol on cocaine-induced taste aversions under conditions similar to those that resulted in attenuated place preferences. Specifically, Experiments 1 and 2 assessed the effects of alcohol (0.5 g/kg) on taste aversions induced by 20, 30 and 40 mg/kg cocaine. Experiment 3 examined the role of intertrial interval in the effects of alcohol (0.5 g/kg) on cocaine (30 mg/kg) taste aversions. In Experiments 1 and 2, cocaine was effective at conditioning aversions. Alcohol produced no measurable effect. Combining cocaine and alcohol produced no greater aversion than cocaine alone (and, in fact, weakened aversions at the lowest dose of cocaine). In Experiment 3, varying the intertrial interval from 3 days (as in the case of Experiments 1 and 2) to 1 day (a procedure identical to that in which alcohol attenuated cocaine place preferences) resulted in significant alcohol- and cocaine-induced taste aversions. Nonetheless, alcohol remained ineffective in potentiating cocaine aversions. Thus, under these conditions alcohol does not potentiate cocaine's aversiveness. These results were discussed in terms of their implication for the effects of alcohol on cocaine-induced place preferences. Further, the effects of alcohol on place preferences conditioned by cocaine were discussed in relation to other assessments of the effects of alcohol on the affective properties of cocaine and the implications of these interactions for alcohol and cocaine co-use.     

Conditioned taste aversion induced in rats by intracerebral or systemic administration of monoamine oxidase inhibitors

Conditioned taste aversion (CTA) elicited by systemic or intracerebral application of the monoamine oxidase inhibitors clorgyline (C), pargyline (P) or deprenyl (D) was studied in 402 rats. Water-deprived animals were allowed 15 min access to 0.1% sodium saccharin (CS) followed 10 min later by IP or by intracerebral injection of the drug. In the latter case, the animals were anesthetized 5 min after saccharin drinking with pentobarbital and the drug was stereotaxically injected (1 l/min, 1–2 l) into the target structure. CTA was assessed in a two-choice retention test performed 2 days later. A geometric progression of three to six dosages applied to groups of rats (n=10) was employed to establish the effective doses of the drugs which were 4, 20 and 32 mg/kg with IP and 2.5, 10 and 80 g per rat with intracerebral (n. raphé magnus) injections of C, P, and D, respectively. The ratios of intracerebral to systemic dosages eliciting comparable CTA were 1:300 for C, 1:800 for P and 1:100 for D. Injections of 2.5 g C and 10 g P into the mesencephalic reticular formation, medial hypothalamus and cerebral cortex were ineffective, as were injections of 10 g P into the nucleus of the solitary tract and cerebellum. The results indicate that CTA is elicited more efficiently by inhibition of monoamine oxidase A (selectively inhibited by C) than of monoamine oxidase B (selectively inhibited by D).     

Conditioned taste aversion induced by ethanol in alcohol-preferring rats: influence of the method of ethanol administration.

A recent study of our group has shown that ethanol evokes conditioned place preference (CPP) in Marchigian Sardinian alcohol-preferring (msP) rats following intragastric (IG) administration by means of an indwelling IG catheter, but not following administration by gavage or by intraperitoneal (IP) injection. The present study evaluated in ethanol-naive msP rats the influence of the method of administration (IG injection by indwelling catheter vs. IP injection) on ethanol-induced conditioned taste aversion (CTA). The dose of 0.35 g/kg of ethanol did not evoke aversion either by IG or by IP administration. Following IG injection, 0.7 g/kg of ethanol, the amount that msP rats voluntarily ingest in a short (2-5 min) drinking episode, did not evoke CTA, and 1.5 g/kg induced a modest CTA. On the other hand, IP injection of 0.7 g/kg of ethanol evoked CTA, and 1.5 g/kg induced a very pronounced CTA. These findings show that the aversive properties of ethanol in msP rats are influenced by the method of administration, and suggest that the IG injection by catheter may reveal more faithfully than the IP injection the motivational properties of amounts of ethanol that alcohol-preferring rats voluntarily ingest.