Stimulation of serotonin1B receptors induces conditioned place aversion and facilitates cocaine place conditioning in rats

RATIONALE: Changes in serotonin(1B) (5-HT(1B)) receptor function appear to modify the reinforcing properties of cocaine, but the direction of this effect is not completely clear. Pharmacological stimulation of 5-HT(1B) enhanced the rewarding properties of self-administered cocaine while attenuating the threshold-reducing effect of cocaine in the intracerebral brain stimulation procedure. OBJECTIVE: The present study investigates how pharmacological modification of 5-HT(1B) receptor-mediated neurotransmission influence cocaine motivational properties in the conditioned place preference paradigm in rats. METHODS: In separate groups of rats the motivational properties of CP 94,253, a selective 5-HT(1B) agonist, or GR 127935, a 5-HT(1B/D) receptor partial agonist, given alone or in combination, were determined. To evaluate their influence on cocaine-induced place conditioning, CP 94,253, that was found to be aversive, was given every day before each conditioning session, while GR 127935, which given alone had no effect, was administered only before cocaine conditioning sessions. RESULTS: CP 94,253, injected IP at 2.5 and 10 (but not 0.5) mg/kg produced place aversion in the place conditioning paradigm. The aversive effect of 2.5 mg/kg CP 94,253 was completely reversed by 10 mg/kg SC GR 127935. Given before every conditioning session, CP 94,253 did not modify place conditioning by four injections of 10 mg/kg cocaine but at 2.5 mg/kg it potentiated a sub-threshold dose of cocaine. The place preference caused by these two drugs was completely reversed by 10 mg/kg GR 127935. The antagonism by GR 127935 of CP 94,253's effects was shown not to be due to the induction of state-dependent effects. CONCLUSION: The results suggest that stimulation of 5-HT(1B) receptors causes place aversion, and enhances the effect of low doses of cocaine in the conditioned place preference paradigm.     

Differential involvement of cortical muscarinic and NMDA receptors in short- and long-term taste aversion memory

In conditioned taste aversion, an animal avoids a taste previously associated with toxic effects, and this aversive memory formation requires an intact insular cortex. In this paper, we investigated the possible differential involvement of cholinergic and glutamatergic receptors in the insular cortex in short-term memory (STM) and long-term memory (LTM) of taste aversion in rats. Taste aversion was induced by intraperitoneal administration of lithium chloride (a malaise-inducing drug) 15 min after experience with an unfamiliar taste. In order to test STM and LTM of taste aversion, taste stimulus was again presented 4 h and 72 h after lithium injection, respectively. During the acquisition, microinjection of the muscarinic antagonist, scopolamine, in the insular cortex before, but not after, the presentation of the new taste, abolished STM as well as LTM. Blockade of the NMDA receptor, in the insular cortex, by AP5 before, but not after, the presentation of the taste stimulus, impaired LTM but left STM intact. Moreover, when injected 1 h after malaise induction (i.e., during taste-illness association), AP5 disrupted both STM and LTM. These results suggest that activation of muscarinic receptors in the insular cortex is involved in the acquisition of taste memory, whereas NMDA receptors participate in taste memory consolidation. These data demonstrate that different neurochemical mechanisms subserve different memory phases. NMDA receptors are also probably involved in processing the visceral input, thus allowing subsequent taste-illness association. This indicates that in the same cortical area the same neurotransmitter system can be involved in distinct processes: taste memory consolidation vs. taste-illness association.     

Lateral parabrachial lesions disrupt paraoxon-induced conditioned flavor avoidance.

Preliminary clinical evidence obtained in Gulf War veterans and patients suffering multiple chemical sensitivity points to the existence of a potential link between environmental exposure to organosphosphates (OPs) and the emergence of unspecific sickness syndromes in which associative Pavlovian conditioning might be partly involved. A laboratory animal model might be a useful tool for analyzing the involvement of conditioning in sickness syndromes potentially linked to OP poisoning. The first objective in the present study was to determine if paraoxon (PX), the neuroactive metabolite of the OP parathion, elicits a conditioned avoidance response to a novel stimulus (a taste-odor compound) in a conditioned flavor aversion procedure. Data obtained in Experiment 1 show conditioned flavor avoidance, demonstrative of the associative nature of the sickness properties of PX. The second objective was to characterize the nature of the specific physiological cue serving as the unconditioned stimulus in PX-induced conditioned avoidance. Despite PX administration did induce cholinergic hyperactivity, as measured by body hypothermia and increased jaw movements, lesions of the lateral parabrachial area (lPB) disrupted PX-elicited flavor avoidance responses, indicating that cholinergic signs were not sufficient as unconditioned stimuli supporting avoidance responses. Given that lPB neural integrity is necessary to process aversive interoceptive information, disruption of conditioned flavor avoidance as a result of lPB lesions is consistent with a central interruption of interoceptive processing in PX-poisoned animals. Data are discussed under the light of the hypothesis claiming the importance of associative processes and noncholinesterase targets in sickness syndromes potentially induced by OP exposure.     

安全学习对大鼠中毒性伙伴效应的影响

目的探讨安全学习是否能阻碍中毒伙伴效应的形成,从而为有害动物防制提供有益的思路。方法实验用成年雄性Wistar大鼠24只,分为对照组、条件性味觉厌恶(CTA)组、安全学习组、观察学习组,其中,对照组单独饲养,其他3组饲养在具有三隔室的铁笼内以便相互作用;CTA组和安全学习组在摄取糖精溶液后,腹腔注射或者不注射LiCl使其分别建立对糖精的CTA和安全学习,观察学习组不做处理;两瓶法测定每只大鼠对糖精溶液相对摄取量。结果对照组、CTA组、安全学习组和观察学习组的糖精溶液嗜好比分别为65.18%、2.12%、86.78%和42.36%,各组之间的差异均具有统计学意义。结论安全学习能有效阻止中毒伙伴效应的发生。     

Lesions of the olfactory pathways affecting neophobia and learned aversion differentially

The contribution of ascending olfactory pathways in neophobia and learned aversion to the same food was investigated in male rats bearing lesions of both olfactory peduncles, or one olfactory peduncle and the opposite lateral olfactory tract or anterior limb of the anterior commissure. The animals were fed on usual stock diet (S) offered as a choice with novel vanilla food (V) on test days: during neophobia (N), then before and after aversive conditioning (Aa, At). Daily food intake was measured, and the preference was expressed as V/(V + S). Experiment 1 included a neophobia test, before aversive conditioning (3 mEq/kg LiCl, i.p.). In Experiment 2, aversion only was studied (0.9 mEq/kg). In the neophobia test, the preference ratio was 7% in unoperated controls, and 43-52% in the 3 lesioned groups. The same controls had preference ratios equal to 64% and 22%, before and after aversive learning. Similar drops were observed for any lesioned group in Expt. 1. The decrease was less obvious, although significant, in rats of Expt. 2 with asymmetric lesions; those with both olfactory peduncles cut through maintained the same preference ratio (48%) before and after LiCl treatment. The data are interpreted assuming that: (1) lateral olfactory tract and anterior commissure both contribute to information processing in neophobia and aversion; (2) olfactory cues subserve neophobia prepotently; and (3) one cannot account for the sensory determinism of neophobia and aversion calling for a single mechanism.     

The role of orosensory stimuli from ethanol and blood-alcohol levels in producing conditioned taste aversion in the rat

A taste-aversion paradigm was used to demonstrate that aversive consequences accompany the rapid oral ingestion of 5% (v/v) ethanol solutions. The learned taste aversion resulted from five 10-min self-administrations of alcohol mixed with an originally preferred flavor at a dosage of 1.69 g alcohol/kg body weight/day. In contrast, when the consumption of the alcohol solution was distributed throughout the day, a conditioned aversion was not obtained. This outcome was observed even though the distributed drinking animals were exposed to more orosensory stimuli and ingested more g/kg than the 10-min animals. The observation that those animals that drank their daily fluid in 10 min demonstrated higher peak blood-alcohol levels than the distributed animals supports the conclusion that a centrally mediated aversive state of inebriation must be present to produce a conditioned aversion.     

Peripheral injections of vasopressin control behavior by way of interoceptive signals for hypertension

The stimulus properties of peripheral injections of vasopressin were assessed using conditioned taste aversion techniques. Conditioned taste aversion induced by vasopressin was blocked by prior exposure to vasopressin but not to another aversive agent, apomorphine. Prior exposure to behaviorally equivalent doses of another hypertensive agent, angiotensin II, blocked also conditioned taste aversion induced by vasopressin and this effect was fully reciprocal, since prior exposure to AVP blocked the aversive effect of angiotensin II. The protection offered by prior exposure to angiotensin II was not due to an endogenous release of AVP since the aversive properties of angiotensin II were not blocked by administration of a specific antagonist of the vasopressor effects of vasopressin. These data suggest that the interoceptive cues which are responsible for the conditioned taste aversion induced by vasopressin are related to the hypertensive action of this peptide.     

GAZE AVERSION IN AUTISTIC AND NORMAL CHILDREN

Autistic children rarely engage in eye contact, and whilst observation suggests this is due to a specific avoidance of eye contact, some experimental studies have challenged this. In this study the effects on autistic and normal children of an adult looking at them with both eyes, with one eye covered, or apparently not looking at them (both eyes covered) were investigated. As expected, autistic children looked more at the adult with his eyes covered, and also engaged in less flight behaviour. They looked less when two eyes were exposed than one, confirming the potency of the two-eye pattern in provoking gaze aversion. Normal children engaged in much more eye contact than the autistic children, with fewer flight behaviours and stereotypies, supporting the hypothesis that autistic children are predominantly flight motivated. Other, sometimes conflicting, results of previous studies are discussed. Teachers and nurses are recommended not to make efforts to engage autistic children even in friendly eye contact as this provokes more flight behaviour.     

NaCl and LiCl efficacy in the induction of aversion for quinine and saccharin solutions immediately following injection

Rats 24-hr water deprived were injected IP with a fixed amount (10 ml/kg) of solutions of various concentrations of LiCl and NaCl in dosage ranges which in previous experiments either increased or had no effect on water intake. Intake of 0.01% QHCl decreased with increasing concentrations of both NaCl and LiCl. On a molar basis, LiCl was more effective. LiCl also produced an aversion to a palatable solution, 0.1% sodium saccharin; however, NaCl produced no aversion over the dosage range which can be tolerated by the animals.