Involvement of dopamine in the aversive stimulus properties of cocaine in rats

Previous studies of cocaine self-administration have demonstrated central dopaminergic involvement in cocaine's positive reinforcing properties. The present study reports the ability of pimozide, a dopamine receptor antagonist, to attenuate a conditioned taste aversion induced by repeated injections of cocaine. Rats placed on a daily water deprivation schedule were subsequently presented with a novel saccharin taste in their drinking fluid immediately followed by administration of four 9 mg/kg injections of cocaine spaced at 20 min intervals. These animals exhibited a reduction in saccharin intake on subsequent presentations. Animals pretreated with pimozide 90 min prior to the saccharin-cocaine pairings failed to show this reduction. In a second experiment using an identical procedure, repeated injections of lithium chloride were shown to induce a CTA both in pimozide-pretreated and control animals. The results of these two experiments are consistent with the notion that a functional relationship may exist between neurochemical mechanisms underlying both the aversive (CTA-inducing) and positive reinforcing properties of self-administered drugs such as cocaine.     

Ovariectomy fails to affect rats' quinine aversion

Three studies investigated the effects of ovariectomy on the intake of quinine solutions. Despite significant elevations of body weight due to surgery, no change in quinine preference was noted. Varying the age of surgery (prepuberty, postpuberty, and adulthood), age of testing, and time between these events did not alter the basic findings.     

Chin rub CRs are elicited by flavors associated with apomorphine, scopolamine, methscopolamine, physostigmine and neostigmine

Three experiments were conducted in order to determine the pattern of behavioral conditioned responses (CRs) elicited by flavors paired with each of various drugs which effectively establish avoidance of a flavored solution. Each of the drugs employed supported both chin rub CRs and avoidance of a flavored solution. Experiment 1 employed apomorphine, a classic emetic agent which pharmacologically acts as a dopaminergic agonist. Experiment 2 and 3 employed cholinergic agonists and antagonists which were either peripherally or both peripherally and centrally acting agents. The results suggest that chin rub CRs may be produced by means of the activation of a system which is peripheral to the CNS. Furthermore, flavor avoidance produced by drugs which support chin rub CRs may be mediated by a shift in the hedonic rating of the flavored solution; whereas, flavor avoidance produced by drugs which do not support chin rub CRs is probably mediated by a mechanism other than a hedonic shift.     

A bioassay of ethanol-dependence in rats

A bioassay for the quantitative assessment of ethanol dependence in rat is proposed. It is based upon the alleviation by ethanol of the withdrawal syndrome in previously intoxicated animals. The conditioning by ethanol of a taste preference, linearly related to the duration of the previous chronic intoxication, provides a reliable measure of the level of ethanol dependence. In addition, the results display the neurobehavioural mechanism by which self-maintained intoxication is established in physically dependent rats and humans.     

Using profiles of saccharin and water drinking to detect and discriminate actions of drugs and toxicants

Experiments were conducted to investigate the feasibility of using the pattern of saccharin and water drinking to detect acute and chronic administration of drugs and toxicants. Procedural variables were found to be crucial. When rats were naive for the saccharin drinking fluid, a single injection of LiCl or 2-deoxyglucose produced persistant saccharin aversion. Hypertonic saline produced only a transient saccharin aversion. If rats were pre-exposed to saccharin, the 2-deoxyglucose injection and hypertonic NaCl produced an increase in saccharin drinking but LiCl was without effect. Several types of chronic treatment were given to saccharin-experienced rats. Chronic 2-deoxyglucose, LiCl, and Pb administration produced gradually developing saccharin aversion and qualitatively different patterns of saccharin and water drinking. Chronic administration of hypertonic NaCl or insulin or chronic food deprivation had no impact on saccharin preference. It was concluded that patterns of saccharin and water drinking can be used to detect the administration of a drug or toxicant and perhaps even the time course of action, but may not detect a substance given previous to saccharin, perhaps because the animal cannot associate these now familiar perturbations with the novel saccharin solution. This means that existing toxic states may not be detected by using saccharin preference as a probe.     

Effects of antiemetics on the acquisition and recall of radiation- and lithium chloride-induced conditioned taste aversions

A series of experiments were run to evaluate the effect of antiemetics on the acquisition and recall of a conditioned taste aversion induced by exposure to ionizing radiation or by injection of lithium chloride. Groups of male rats were exposed to 100 rad gamma radiation or 3 mEq/kg lithium chloride following consumption of a 10% sucrose solution. They were then injected with saline or with one of three antiemetics (prochlorperazine, trimethobenzamide, or cyclizine) at dose levels that have been reported to be effective in attenuating a previously acquired lithium chloride-induced taste aversion. The pretreatments with antiemetics had no effect on the acquisition or recall of either the lithium chloride- or radiation-induced taste aversion. The data suggest that antiemetics do not disrupt lithium chloride-induced taste aversions as previously reported, nor do they effect radiation-induced taste aversion learning.     

Cross-familiarisation conditioned taste aversion procedure as a method to reveal stimulus resemblance between drugs: studies on the 5-HT1A agonist 8-OHDPAT

In the present study a cross-familiarisation conditioned taste aversion (CTA) paradigm was utilized to reveal stimulus resemblance between the selective 5-HT_1A agonist 8-OHDPAT and a variety of serotonergic and non-serotonergic drugs. In male mice, a 0.22 mg/kg dose of 8-OHDPAT was used as the reference compound inducing CTA. Dose-dependent effects of pre-exposure to 24 different test drugs on the magnitude of the 8-OHDPAT-induced CTA were tested as a measure for stimulus similarity between these test drugs and 8-OHDPAT (the reference compound). Pre-exposure to 8-OHDPAT itself, ipsapirone, buspirone, RU 24969, sertraline,d-amphetamine, LSD, metergoline and idazoxan effectively prevented the development of CTA induced by 8-OHDPAT. Pre-exposure to apomorphine, diazepam, SCH 23390, LiCl, spiperone, DOI, spiroxatrine, umespirone, pindolol,mCPP, haloperidol, MK 212, clonidine, quipazine and also 5-MeODMT was not effective in completely abolishing the CTA produced by 8-OHDPAT. It is concluded from these results that the relatively simple and fast cross-familiarisation taste aversion method is a suitable paradigm to study similarities in stimulus properties of different drugs.     

Phencyclidine and behavior: I. Sensory-motor function,activity level,taste aversion and water intake

Phencyclidine (PCP) injections in rats at doses of 4 mg/kg increased activity level, which might have been a function of impaired habituation. At doses of 8 mg/kg PCP produced a marked reduction in activity level. At doses of 12 mg/kg and above there were profound disruptive effects in detection of odors, visual square and touch measures, and performance of placing reflexes requiring visuo-motor coordination, righting, grasping reflexes, and equilibrium. Decreases in water intake occurred only at higher dose levels of PCP (16 and 24 mg/kg). On a qualitative basis the changes observed in rats are similar to changes described for humans.