The effects of ACTH- and vasopressin- analogues on CO2-induced retrograde amnesia in rats

Amnesia for a one-trial step-through passive avoidance response was induced in rats by application of CO₂ until respiratory arrest occurred. The ACTH-analogue ACTH_4–10 alleviated the amnesia when administered 1 hr prior to the retrieval test but not when given 1 hr prior to the acquisition trial. The behaviourally inert ACTH-analogue ACTH_11–24 appeared to have no effect on the amnesia. The vasopressin-analogue desglycinamide lysine vasopressin (DG-LVP) antagonized the amnesia when administered 1 hr prior to the acquisition trial or 1 hr prior to the test trial. The relevance of these date to present theories on amnesia is discussed.     

Anti-amnesic effect of ACTH4-10: its independence of the nature of the amnesic agent and the behavioral test.

It was found previously that ACTH_4–10 is able to alleviate the CO₂-induced retrograde amnesia for a step-through passive avoidance response when injected into rats 1 hr prior to the retrieval test. The present investigation was undertaken to establish whether ACTH_4–10 has a similar effect if a different amnesia agent and a different behavioral task are used. It appeared that electroconvulsive shock induced amnesia for a one-trial thirst-motivated response. This amnesia could be reduced by administration of ACTH_4–10 1 hr prior to the retrieval test. Administration of ACTH_4–10 1 hr prior to the acquisition was ineffective. It was concluded that ACTH_4–10 exerts a retrieval-promoting effect independent of the nature of the amnesic agent and the behavioral task.     

Passive avoidance learning in the crab Chasmagnathus granulatus

Male crabs Chasmagnathus granulatus were trained by means of a method similar to the standard inhibitory avoidance technique widely used in vertebrates. Each crab was placed in the dark compartment (DC) of a double-chamber device, allowed to move towards the light compartment (LC) and latency to enter measured. Experimental crabs received a shock in LC, but controls were not punished. After 1 min, both experimental and control crabs were free to return to DC. On completion of 1, 2, 3 or 24 hr intertrial interval in DC a retention test was administered and latency to enter LC was measured. A single trial was proven enough to establish a LC-shock association that was detected up to 3 hr later, but no retention was proved after 24 hr. Memory was disrupted when crabs were removed from the apparatus during the 3 hr intertrial interval. Similarities and differences between the passive avoidance method used with crabs and that used with vertebrates are discussed.     

Differential effects of ACTH4-10, DG-AVP, and DG-OXT on heart rate and passive avoidance behavior in rats.

A computerized telemetry system was used to monitor heart rate (HR), core temperature (CT), and gross locomotor activity in rats treated with saline or neuropeptides during a passive avoidance behavior task. Rats were exposed to a single mild footshock (0.15 mA, for 3 s). Retention tests were conducted at 24 and 48 h after the learning trial. One h prior to the 24-h retention test, each rat received one of the following treatments (SC): saline (SAL), desglycinamide [Arg8]-vasopressin (DG-AVP), ACTH4-10, or desglycinamide-oxytocin (DG-OXT), at a dose of 3 micrograms/rat for DG-AVP and DG-OXT, and 50 micrograms/rat for ACTH4-10. Rats treated with SAL showed a modest increase in avoidance latency accompanied by bradycardia at both retention tests. Rats receiving DG-AVP retained the highest avoidance latency among the experimental groups at both the 24- and 48-h retention test. These rats showed a decrease in HR of the same magnitude as the SAL-treated animals at both retention tests. Rats treated with ACTH4-10 showed an increase in avoidance latency during the 24-h but not during the 48-h retention test. In addition, following ACTH4-10 treatment, a tachycardiac response was found during the 24-h retention test. DG-OXT induced both behavioral and cardiac responses opposite to those found in rats given DG-AVP. CT gradually increased while the rats remained on the platform, irrespective of the treatment. Changes in HR and CT were not influenced by somatomotor activity, as no difference in gross locomotor activity was found among the groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Opiate antagonists suppress ACTH1–24-induced excessive grooming in the rat

Intraventricular injection of ACTH_1–24 in rats induces excessive grooming behavior, and subsequent peripheral administration of specific opiate antagonists suppresses this peptide-induced grooming response. Intraventricular injection of morphine mimics both in intact and hypophysectomized rats' — to a certain extent — peptide-induced grooming. The results suggest similarities in the interaction of morphine and ACTH_1–24 with central nervous structures.     

Sexual dimorphism in passive avoidance behavior of rats: Relation to body weight,age, shock intensity and retention interval

Female rats were inferior to age- and weight-matched males in the retention of a step-through type passive avoidance response 24 and 48 hr after the learning. This sex difference could be observed at different intensities of foot shock which was used as aversive stimulus during the single learning trial. Additionally, unlike in males, retention of the passive avoidance response in the females was not the function of shock intensity. Male and female rats, however, showed similar passive avoidance if tested immediately after the learning trial. The results suggest the existence of sexual dimorphism in memory processes.     

Passive avoidance learning in young chicks: Time of day effects

Day old chicks hatched from 17±1 day old fertilised eggs under a 14:10 L/D cycle (lights on:0700 hr; lights off:2100 hr) were trained at 0800, 1200, 1600 and 2000 hr on day 1 posthatch on a single trial passive discriminated avoidance task and tested for retention 24 hr later. Chicks trained at 0800, 1200 and 1600 hr showed evidence of learning but differed in the nature of what was remembered. Discrimination memory is best when training took place at 1200 hr but poorest at 1600 hr, when chicks tended to generalise avoidance to a previously non-aversive stimulus. Chicks trained at 0800 hr showed as much discrimination memory as generalised avoidance. At 2000 hr any evidence of avoidance learning was compromised by a naturally high level of avoidance of pecking at this time of day. There was no evidence of systematic variation in locomotor activity during the light period associated with the changes observed in learning and memory. However, control chicks exhibited a high level of pecking activity at 1600 hr relative to the other times. The findings support the possibility that learning of and memory for a single trial passive discriminated avoidance task may be affected by time of day of training. It is suggested that the results may be due to a complex interaction of arousal, pecking activity and time of day.     

Developmental aspects of passive and active avoidance learning in rats

In Experiment 1, groups of rats 16, 19, 25, 32, and 90 to 120 days of age, were tested for retention of a passive avoidance response 2 min or 24 hr following a single training trial. Passive avoidance learning improved markedly with age, and retention over a 24-hr interval was complete for all age groups. In Experiment 2, rats 19, 25, 32, and 90 to 120 days of age were trained in a simple, active avoidance task. A trials-to-criterion measure indicated that learning was relatively independent of age, although 19-day rats were somewhat inferior to older rats. The occurrence of differences in passive avoidance learning through developmental ranges in age where simple active avoidance is little affected suggests that inhibition of responding may be selectively influenced by maturational variables.     

Attenuation of anoxia-induced retrograde amnesia in rats by a pretraining placebo injection

Rats were given an oral injection of distilled water 35 min before one-trial passive avoidance learning, achieved by punishing a bar-press performance with a single footshock. Immediately after training the rats were submitted to asphyxia-induced anoxia. While the noninjected control group failed to perform an avoidance response 24 hr after the anoxic treatment, the injected group, whose normal bar-press performance remained unchanged after the injection, showed a good retention for the shock event despite the anoxic treatment. These data demonstrate that an injection like other environmental events effect memory elaboration and they do not support the consolidation hypothesis which does not account for such variables.     

Immunocytochemical localization of α-melanocyte stimulating hormone (α-MSH)-like compounds in the rat nervous system

This immunocytochemical study shows that, in addition to the presence of α-MSH in the intermediate lobe of the pituitary, α-MSH-like compounds are present throughout the nervous system: (1) in the cerebrum mainly in association with myelinated structures, in the choroid plexus, and pineal gland, (2) in the cerebellar basket cell fibers, granule cells and white matter, (3) in neurons of the medulla oblongata, (4) in nerve fibers and motoneurons in the spinal cord and (5) in neurites and cell bodies of the dorsal root ganglion cells. No straining was obtained with antibodies against ACTH_1–39 or ACTH_1–24. The α-MSH-like compounds are localized predominently in neurons, and are probably synthetized within the nervous system.     

Changes in heart rate and body temperature during passive avoidance behavior in rats

Heart rate, core temperature and gross locomotor activity during passive avoidance behavior in rats were recorded by a telemetry system connected to a computer data acquisition program. Passive avoidance latency and approach to the dark compartment were evaluated. Rats were assigned to five different groups, i.e., the shock groups that received different intensities of footshock (0.15, 0.25 and 1.0 mA, respectively, for 3 sec), a no footshock control group and a group that had no access to the dark compartment (i.e., no dark compartment control group). Retention tests were carried out 24 and 120 hr after the learning trial. Rats exposed to footshock showed a decrease in heart rate during the first 10 sec of the observation period in both retention tests. An average bradycardia was found in the lowest shock intensity group (0.15 mA) at both the 24- and 120-hr retention test whereas the other two groups (0.25 and 1.0 mA) showed a gradual increase in heart rate. This increase was more pronounced the longer the rats stayed on the platform. Similarly, a gradual rise in core temperature was observed in these rats as well as in the no dark compartment control group. The number of approaches to the dark compartment was significantly depressed in the group exposed to 1.0 mA footshock intensity. Gross locomotor activity was reduced in animals that exhibited maximum avoidance latency. Exposure of rats to the above-described behavioral paradigms induced autonomic activation resulting in changes in heart rate and temperature. These changes were not caused by gross locomotor activity and may thus be related to the various behavioral states.(ABSTRACT TRUNCATED AT 250 WORDS)     

Amygdaloid lesions block the effect of neuropeptides (vasopressin, ACTH4--10) on avoidance behavior.

Lesions in the amygdaloid complex result in an increased activity of rats in open field behavior in that generally more exploration and rearing is observed as compared with sham-operated animals. No effect of the lesion was observed on acquisition and extinction of an active avoidance response, but the amygdala lesions block the inhibitory effect of the neuropeptides vasopressin and ACTH_4–10 on extinction of a conditioned avoidance response.     

Effects of ACTH4--10 on self-stimulation behavior in the rat

The threshold current evoking self-stimulation or multiples of this current was used to investigate the effect of ACTH_4–10 on response performance for brain stimulation reward in the medial septum (MS) and the medial forebrain bundle (MFB). ACTH_4–10 in a dose of 50 μg administered SC enhanced bar-pressing for low intensity stimulation but failed to change self-stimulation rates when the base-line rate exceeded 100 responses per 6 min. The peptide lowered the threshold for producing self-stimulation but only in the MS. When an ascending sequence of threshold multiples was used within a session, ACTH_4–10 treatment resulted in an increase in response rate at 1.2 and 1.5 threshold multiples and a decrease at 3.0 times the threshold but only in the MS. The results indicate that ACTH_4–10 facilitated response performance at a low response rate by enhancing the rewarding effect of brain stimulation. Furthermore, the peptide changed the response pattern which normally followed reinforcement shift in the MS.     

Modification by environmental conditions of retrograde amnesia produced by ECS

A single ECS following one trial appetitive learning produced retrograde amnesia after 24–72 hr in rats housed individually in a colony during the ECS-retention trial interval. In animals given the same treatment procedures and housed individually in a dark chamber with a constant level of background noise, no retrograde amnesia following ECS was noted. These results suggest that varying environmental conditions during the ECS-retention interval may eliminate or enhance retrograde amnesia. Further, these deficits in retention appear to be retrieval deficits which are associated with events producing brain dysfunction and loss of retention.     

Behavioral and endocrine responses of rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain)

Behavioral and endocrine profiles were established of homozygous (HO-DI) and heterozygous (HE-DI) rats with hereditary hypothalamic diabetes insipidus in comparison to Wistar strain rats. HO-DI rats were inferior in acquiring and maintaining active and passive avoidance behavior. Behavioral deficits were most obvious in a step-through one-trial learning passive avoidance test and least in multiple trial one way active avoidance test. Plasma corticosterone levels determined after the retention test appeared to be closely related to the passive avoidance behavior of the HO-DI rats. Passive avoidance immediately after the single learning trial was associated with elevated plasma corticosterone level; absence of avoidance and absence in plasma corticosterone elevation was observed 24 hr after learning. These observations are compatible with the hypothesis that vasopressin is involved in the consolidation and/or retrieval of learned responses. Differences between HO-DI and Wistar rats in open field behavior, in response threshold to electric footshock, and in a number of somatic endocrine parameters are reported and discussed.     

Factors and common conditions associated with adolescent dietary supplement use: an analysis of the National Health and Nutrition Examination Survey (NHANES)

Background

Studies show that electroacupuncture (EA) has beneficial effects in patients with inflammatory diseases. This study investigated the mechanisms of EA anti-inflammation, using a rat model of complete Freund's adjuvant (CFA)-induced hind paw inflammation and hyperalgesia.

Design

Four experiments were conducted on male Sprague-Dawley rats (n = 6–7/per group). Inflammation was induced by injecting CFA into the plantar surface of one hind paw. Experiment 1 examined whether EA increases plasma adrenocorticotropic hormone (ACTH) levels. Experiments 2 and 3 studied the effects of the ACTH and corticotropin-releasing hormone (CRH) receptor antagonists, ACTH_(11–24) and astressin, on the EA anti-edema. Experiment 4 determined whether EA activates CRH neurons in the paraventricular nucleus of the hypothalammus. EA treatment, 10 Hz at 3 mA and 0.1 ms pulse width, was given twice for 20 min each, once immediately post and again 2 hr post-CFA. Plasma ACTH levels, paw thickness, and paw withdrawal latency to a noxious thermal stimulus were measured 2 h and 5 h after the CFA.

Results

EA significantly increased ACTH levels 5 h (2 folds) after CFA compared to sham EA control, but EA alone in naive rats and CFA alone did not induce significant increases in ACTH. ACTH_(11–24) and astressin blocked EA anti-edema but not EA anti-hyperalgesia. EA induced phosphorylation of NR1, an essential subunit of the N-methyl-D-aspartic acid (NMDA) receptor, in CRH-containing neurons of the paraventricular nucleus.

Conclusion

The data demonstrate that EA activates CRH neurons to significantly increase plasma ACTH levels and suppress edema through CRH and ACTH receptors in a rat model of inflammation.     

Guinea pig medial vestibular nucleus neurons in vitro respond to ACTH4–10 at picomolar concentrations

Summary The responses of single guinea pig medial vestibular nucleus (MVN) neurons in vitro to adrenocorticotropic hormone, fragment 4–10 (ACTH_4–10) were recorded extracellularly. In coronal slices and in the isolated MVN, neurons were found which responded to ACTH_4–10 at picomolar concentrations (10^-12M), indicating that ACTH_4–10 acts directly on MVN neurons and suggesting the possibility that ACTH_4–10 may act as a neurotransmitter in the MVN. In most cases where neurons responded to ACTH_4–10 (37/74 neurons), the effect was a decrease in firing. Whether or not the depressive action of ACTH_4–10 on the firing rate of MVN neurons in vitro is related to the acceleration of behavioral recovery from unilateral labyrinthectomy (vestibular compensation), which has been reported previously (Flohr and Luneburg 1982; Igarashi et al. 1985), is unclear.     

Microinjection of arginine8-vasopressin antiserum into the dorsal hippocampus attenuates passive avoidance behavior in rats

Antiserum to arginine⁸-vasopressin was microinjected bilaterally into the dentate gyrus of the dorsal hippocampus and the effect on passive avoidance behavior was studied. After the single learning trial of a passive avoidance response, immediate bilateral injection of 1 μl antiserum (diluted to $\text{1}\text{50}$) attenuated passive avoidance responding 24 hr later. In immunocytochemical control studies with injection of undiluted antiserum into the dentate gyrus a spreading was observed towards the ventral hippocampus and the dorsal septum. Additionally, administration into the lateral ventricle of 2 μl of $\text{1}\text{50}$ dilution of the antiserum did not affect the behavior. For an attenuation of passive avoidance behavior via intraventricular injection, 2 μl of a $\text{1}\text{10}$ dilution of anti-AVP was required. These data suggest that endogenous vasopressin in the septo-hippocampal system might be involved in memory processes.     

Comparison of the effects of ACTH and lysine vasopressin on avoidance-of-attack in mice.

Single injections of either ACTH or lysine vasopressin (LVP) were administered to mice at one of three times: either (1) prior to training in a passive avoidance situation where the aversive stimulus is attack by a trained fighter mouse, (2) just following acquisition of the passive avoidance response, or (3) just prior to a first retention test at 24 hr after acquisition. Retention of the avoidance response also was assessed at 48 and 240 hr postacquisition. Both ACTH and LVP enhanced retention of the response, although their effects were different in character. ACTH's effects were relatively short-lived: the facilitatory effect of ACTH treatment was evident at the first (24 hr) retention test but had disappeared by the 240 hr test. On the other hand, LVP's effects became apparent later (at 48 hr) but lasted through the 240 hr test. In addition, the critical times for their administration were different: ACTH treatment enhanced avoidance retention no matter when the hormone was administered, whereas LVP only enhanced retention if this hormone had been administered after acquisition or prior to the first retention test; LVP treatment before acquisition did not affect avoidance-of-attack. The effects of ACTH and LVP on avoidance-of-attack are basically similar in form to the effects of these hormones on avoidance-of-shock.     

Developmental aspects of 2-way shuttlebox avoidance in the spontaneously hypertensive and normotensive rat

In Experiment I, male and female rats from the spontaneously hypertensive (SHR) and Wistar-Kyoto (WKYN) normotensive strains were given 1 session of 2-way shuttlebox avoidance training at 25–26, 35–36, or 45–46 days of age. The avoidance training was preceded by a pretest which consisted of 10 presentations of the compound conditioned stimulus alone in order to assess any differential tendency of the 2 strains to respond to the presentation of novel stimuli. The WKYN rats made a significantly higher number of pretest avoidance responses and achieved a higher level of avoidance performance than SHR rats. In addition, during the pretest, WKYN rats were more active and had a shorter 1st trial latency. In Experiment II, the pretest phase was replicated with a manipulation of the intensity of the auditory cue. Although the WKYN rats had a higher rate of pretest avoidance than SHR rats, the rate of pretest avoidances increased with intensity in both strains. The WKYN rats had a shorter 1st trial latency and a shorter median latency for the 10 trials and were more active than SHR rats during the pretest. These results relate to age-independent behavioral characteristics of these strains and the question of reactivity to environmental stimulation.