PubMed Health⌕ Search

Biomedical subjects

I P Stolerman

Publications and source records attributed to I P Stolerman.

At least 109 records · Page 6Linked to original sources

Characteristics of conditioned taste aversion produced by nicotine in rats.

1 Nicotine produced conditioned taste aversions in rats which were directly related to the dose of nicotine and to the number of conditioning trials. 2 The tobacco alkaloid (-)-nicotine was four to five times as potent as its stereoisomer, (+)-nicotine. 3 Mecamylamine but not hexamethonium blocked the development of taste aversions produced by nicotine. 4 Mecamylamine did not block the development of taste aversions produced by apomorphine. 5 Prolonged treatment with mecamylamine prior to conditioning did not produce supersensitivity to nicotine.

Amphetamine↗

Does conditioned nausea mediate drug-induced conditioned taste aversion?

Two antiemetic drugs were tested on the expression of taste aversions previously conditioned in rats with lithium, amphetamine or morphine. Neither prochlorperazine nor scopolamine administered prior to testing attenuated established aversions, although both drugs are known to have antiemetic effects in other species. Negative findings were obtained with a range of dose of prochlorperazine and scopolamine, with strong and weak aversions, with one- and two-stimulus tests, in a repeated one-stimulus extinction procedure, with between- and within-group designs and with hooded, albino, male and female rats. The results do not support the widely accepted hypothesis that conditioned nausea mediates conditioned taste aversion.

Amphetamine↗

Role of training conditions in discrimination of central nervous system stimulants by rats.

Amphetamine and some relate compounds were compared in rats trained to discriminate (+)-amphetamine (0.4, 1.0 or 1.6 mg/kg) or cocaine (10.0 mg/kg) from the non drug condition in a standard, two-bar procedure with food reinforcement (n=5-6). Amphetamine and cocaine were generalized completely with each other, in most cases at dose levels which did not greatly reduce the overall numbers of responses. The ED50 values for amphetamine and cocaine varied with the drug and dose used for training, and it was concluded that the stimuli produced by the two drugs were similar but may not be identical. There was an excellent correlation between ED50 values derived from indices of bar selection and percentage-responding on the drug-appropriate bar. Apomorphine was generalized with amphetamine only in the rats trained with the higher doses of amphetamine, and only when administered in doses which greatly reduced the overall number of responses. Para-hydroxyamphetamine increased responding on the drug-appropriate bar only when administered in high doses to the rats trained with the lowest dose of amphetamine (0.4 mg/kg). The results strengthen the evidence that the particular drug and dose level used for training can significantly affect the outcome of generalization tests, and challenge the notion that the discriminability of drugs is an immutable property that is amenable to absolute measurement.

Amphetamine↗

Conditioned taste aversion and operant behavior in rats: effects of cocaine, apomorphine and some long-acting derivatives.

Apomorphine and cocaine and their long-acting derivatives, diisobutyrylapomorphine and Win 35,428 (a fluorine-substituted phenyltropane analog of cocaine), were compared for their effects in producing conditioned taste aversions and altering schedule-controlled behavior in rats. The drugs had qualitatively similar effects in both types of experiments; suitable doses of each drug produced marked decreases in consumption of flavored solutions associated with their injection and suppressed key-press responding maintained under a 30-response fixed-ratio scheduled of food presentation. Potency ratios for apomorphine and cocaine relative to their long-acting derivatives were similar in both experiments; Win 35,428 was approximately 34 times more potent than cocaine, whereas apomorphine and diisobutyrylapomorphine did not differ appreciably in potency. Extending the duration of action of cocaine by administering an initial dose of 53 micromol/kg of cocaine followed by two additional doses of 26.5 micromol/kg at 30-min intervals failed to produce a greater degree of taste aversion than administration of only a single dose of 53 micromol/kg of cocaine. The observations with Win 35,428 and diisobutyrylapomorphine confirm previous work with these compounds and extend its generally to other species of animal and types of behaviors. None of the findings support the view that the potency of a drug in producing conditioned taste aversions is correlated with its duration of action.

Animals↗

Factors influencing feeding elicited by intracranial noradrenaline in rats.

An improved design of microcannula was used to inject noradrenaline into discrete areas of the rat hypothalamus. The area of the paraventricular nucleus was shown to be a more effective site than the midlateral anterior hypothalamus for eliciting feeding with noradrenaline (4.8 microgram). The magnitude but not the direction of the effect of noradrenaline on feeding was influenced by the day-night cycle. The facilitating effect of the drug reached significance in the light period but not in the dark period, possibly because the baseline food intake was higher by night than by day. The facilitation of feeding occurred whether the rats were maintained and tested on a diet of solid or liquid food.

Animals↗

Amphetamine-induced hypodipsia and its implications for conditioned taste aversion in rats.

According to the conditioned anorexia hypothesis, conditioned taste aversions occur when flavour stimuli are classically conditioned to the anorexigenic or hypodipsic effects of drugs. The effects on water intake of a range of doses of amphetamine and of several related compounds have therefore been examined in an attempt to correlate their known potentices in tate aversion experiments with their hypodipsic potencies (+)-Amphetamine was more potent than (-)-amphetamine in suppressing water intake but under similar experimental conditions, the isomers were equipotent in the conditioning of taste aversions. Methamphetamine and p-chloromethamphetamine were equipotent in suppressing water intake, but the latter was a more potent agent for conditioning taste aversions. Furthermore, fenfluramine produced taste aversions at doses well below those which suppressed water intake. It was concluded that the ability of the drugs to induce taste aversion was not related to their unconditioned, hypodipsic effects. However, it was confirmed that when drugs with different durations of action are compared for anorexic or hypodipsic potency, the outcome can be greatly influenced by the time over which measurements are made.

Amphetamine↗

Suppression of fixed-interval responding by flavour-amphetamine pairings in rats.

Amphetamine is a potent and very effective drug for conditioning taste aversions, but much less is known about the possible effects of flavour-amphetamine pairings on aspects of behaviour other than eating and drinking. Rats were trained to press bars for water reinforcers delivered on a fixed-interval one-min schedule. Flavoured reinforcers were then substituted for the water and post-session injections of amphetamine (1 mg/kg) were given. Even a single flavour-amphetamine pairing produced some disruption of responding for that flavour, whereas 3 pairings almost completely suppressed responding (both bar-pressing and drinking). In the same rats, flavours paired with saline injections did not suppress responding. Amphetamine (1mg/kg) injected before sessions of responding for plain water disrupted the temporal pattern of fixed interval responding without affecting the total numbers of bar-presses or the amounts of liquid consumed. Omitting primary reinforcement (water) throughout a single session also failed to suppress responding. The conditioned effects of the flavour were therefore different from the effects of either the unconditioned stimulus (amphetamine) or of an extinction procedure.

Amphetamine↗

Amphetamine-induced taste aversion demonstrated with operant behaviour.

Amphetamine can be used to condition strong taste aversions, but little is known about the possible effects of flavour-amphetamine pairings on operant behaviour. Rats were trained to press bars for water reinforcers delivered after every 40 responses (FR 40). Flavoured reinforcers were then substituted for the water and post-session injections of amphetamine (1 mg/kg) were given. Even a single flavour-amphetamine pairing produced some decrement in responding for that flavour, whereas three flavour-amphetamine pairings almost completely suppressed responding. In the same rats, a flavour which was paired with saline injections did not suppress responding. Flavour-amphetamine pairings can therefore have a powerful influence on operant behaviour and the different outcomes of flavour-conditioning and self-administration procedures cannot be attributed simply to the type of response required from the rat.

Animals↗

Factors influencing flavour aversions conditioned with amphetamine in rats.

Rats would not drink distinctively flavoured solutions after their previous ingestion had been followed by injection of amphetamine (1 mg/kg). In the same rats, intake of flavoured solutions followed by saline injections was not suppressed. Providing the rats with cues as to the location of flavoured solutions paired with amphetamine did not alter either the speed of development or the final severity of the aversion. Neither increasing the interval between presentation of the flavour and injection of amphetamine, nor decreasing baseline drinking levels, altered the final degree of aversion. The aversion became progressively weaker as the dose of amphetamine was reduced, but it was detectable at doses as low as 0.1 mg/kg. Further decreases in dose did not enhance intake of flavours paired with amphetamine, even when combined with reductions in baseline drinking brought about by reduced fluid deprivation and flavour palatability. The results are discussed in relation to the conditions in which amphetamine has been shown to exhibit either rewarding or aversive properties.

Animals↗

Interaction of cocaine with chlordiazepoxide assessed by motor activity in mice.

1 Effects of a range of doses of cocaine and chlordiazepoxide given separately and as mixtures were determined on the spontaneous locomotor activity of mice. 2 Cocaine increased locomotor activity (walking) during 3 or 5 min trials in a dose-related manner. 3 Chlordiazepoxide had little effect on the total amount of locomotor activity except for depression at very high doses. A lower dose of chlordiazepoxide increased activity at the beginning of the trials only. 4 Mixtures containing certain doses of cocaine and chlordiazepoxide increased locomotor activity ot a much greater extent than cocaine alone. This high level of activity was manifested throughout 5 min trials. 5 This action of cocaine is similar to that of amphetamine.

Animals↗

Comparative potencies of amphetamine, fenfluramine and related compounds in taste aversion experiments in rats.

1 Rats failed to drink a flavoured solution when its consumption had been followed by injection of amphetamine (conditioned taste aversion).2 There was very little difference between the potencies of (+)- and (-)-amphetamine.3p-Chloromethamphetamine was a more potent aversive agent than methamphetamine.4 Strong taste aversions were also conditioned with other congeners of amphetamine. The rank order of potency was: fenfluramine > chlorphentermine >p-hydroxyamphetamine.5 Cocaine induced only moderate taste aversions, even at high doses.6 Aversive potency did not appear to be correlated with known neurochemical actions of the drugs or with behavioural stimulation, but appeared to be a central action which may have been linked to anorexigenic potency or time course of action.

Amphetamines↗

Comparison of the discriminative stimulus properties of cocaine and amphetamine in rats.

1. Water-deprived rats were trained to press either the left or the right bar in a test chamber according to whether they were injected with a central nervous system stimulant or 0.9% w/v NaCl solution (saline). Correct responses were reinforced with water. 2. Different groups of rats learned to discriminate amphetamine or cocaine from saline. Dose-response curves and ED50 values were then determined in brief test sessions when no responses were reinforced. 3. In a crossover study, cocaine was tested in the rats trained to discriminate amphetamine from saline, and vice versa. The two drugs were largely interchangeable, but the ED50 values were increased, indicating a possible, subtle difference in their discriminative stimulus properties. 4. The results indicate the importance of complete crossover designs in combination with dose response determinations when attempting to classify drugs according to their discriminable properties.

Animals↗

Reactions to cigarettes as a function of nicotine and "tar".

Experiments carried out to examine the effects of nicotine and "tar" on the extent of and subjective reactions to cigarette smoking. It was confirmed that smokers rate commercial, low-nicotine cigarettes as less "strong" and less "satisfying" than their usual brands. Since such cigarettes deliver reduced amounts of tar as well as of nicotine, an experiment to distinguish between the two was carried out with special cigarettes. Ratings of "strength" were directly related to nicotine but were not affected by tar. The numbers of cigarettes smoked fell slightly as their estimated delivery of nicotine increased, but tar had no effect on this index. The urinary excretion of nicotine was correlated with the rated yields of nicotine for the different cigarettes, but there was also evidence that subjects tended to adjust their manner of smoking so as to titrate their doses of nicotine. The results are interpreted as indicating a role for nicotine, but not for tar, in the maintenance of cigarette smoking behavior, and as support for the view that less harmful cigarettes should have a high yield of nicotine relative to tar.

Adult↗