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Biomedical subjects

J E Barrett

Publications and source records attributed to J E Barrett.

At least 109 records · Page 6Linked to original sources
PubMed1985

Effects of serotonin receptor agonists and antagonists on schedule-controlled behavior of squirrel monkeys.

The behavioral effects of the serotonin (5-HT) precursor l-5-hydroxytryptophan (l-5-HTP) and the phenylpiperazine 5-HT agonists 6-chloro-2-(1-piperazinyl)pyrazine (MK-212), 1-(m-trifluromethylphenyl) piperazine (TFMPP), 1-(m-chlorophenyl)piperazine (CPP) and 2-(1-piperazinyl)quinoline (quipazine) were compared with those of the putative 5-HT antagonists metergoline, methysergide, cyproheptadine, cinanserin and ketanserin under a multiple 5-min fixed-interval schedule of food or electric shock presentation in squirrel monkeys. Intramuscular administration of l-5-HTP (0.3-17 mg/kg), MK-212 (0.01-1.0 mg/kg), TFMPP and CPP (0.03-10 mg/kg) produced dose-related decreases in responding under both the food- and shock-presentation schedules. Quipazine differed from the other 5-HT agonists in that it increased shock-maintained behavior at doses (0.1-1.0 mg/kg) that decreased responding maintained by food. The 5-HT antagonists produced mixed behavioral effects. Metergoline (0.03-1.0 mg/kg), cyproheptadine (0.1-1.0 mg/kg) and cinanserin (1.0-10 mg/kg) produced dose-related increases in responding maintained by food, whereas only metergoline and methysergide increased behavior maintained by shock presentation. The prototype 5-HT2-receptor ligand ketanserin (0.3-10 mg/kg) differed from the other 5-HT antagonists in that it decreased behavior maintained by either event. Thus, performances maintained by food or shock presentation reveal both qualitative and quantitative differences in the behavioral effects of 5-HT receptor agonists and antagonists.

5-Hydroxytryptophan↗
PubMed1985

Behavioral studies with anxiolytic drugs. I. Interactions of the benzodiazepine antagonist Ro 15-1788 with chlordiazepoxide, pentobarbital and ethanol.

Lever pressing by squirrel monkeys was maintained under two behavioral procedures known to be sensitive to anxiolytic drugs. Under one procedure, responding maintained by food was suppressed by electric shock (punishment). Under a second procedure, responding was maintained under a multiple schedule in which the first response after 5 min produced either food or shock depending on the stimulus that was present throughout the interval (fixed-interval schedule). Under the punishment schedule, chlordiazepoxide (1.0-100 mg/kg), pentobarbital (1.0-17.0 mg/kg) and ethanol (0.5-2.5 g/kg) increased responding. The benzodiazepine antagonist, Ro 15-1788 (1.0-10.0 mg/kg), which was without behavioral activity when given alone, reversed the effects of chlordiazepoxide in a dose-dependent manner. Ro 15-1788 did not antagonize the effects of pentobarbital or ethanol but potentiated the rate-increasing effects of these compounds. Under the multiple fixed-interval food- or shock-presentation schedule, both chlordiazepoxide and pentobarbital increased responding maintained by food but only decreased responding maintained by shock. Ro 15-1788 antagonized the rate-increasing effects of chlordiazepoxide under the food schedule and reversed the rate-decreasing effects during the shock-presentation schedule; pentobarbital effects were not altered by Ro 15-1788. Certain dose-combinations of chlordiazepoxide and Ro 15-1788 produced large increases in responding maintained by shock, an effect not seen with either drug alone. These studies indicate that Ro 15-1788 antagonizes the behavioral effects of benzodiazepines selectively but not those of other sedative-hypnotic drugs. These results also suggest that Ro 15-1788 may exert certain actions of its own or may unmask other drug effects when given in combination with benzodiazepine and nonbenzodiazepine compounds.

Animals↗
PubMed1985

Effects of serotonin receptor antagonists on punished responding maintained by stimulus-shock termination or food presentation in squirrel monkeys.

The behavioral effects of a series of serotonin (5-HT) receptor antagonists were examined on punished performances maintained by termination of a stimulus correlated with shock (stimulus-shock termination) or by food presentation in squirrel monkeys. Intramuscular administration of metergoline (0.03-0.3 mg/kg), methysergide (0.1-1.0 mg/kg), cyproheptadine (0.1-1.0 mg/kg), mianserin (0.1-10 mg/kg) and cinanserin (1.0-3.0 mg/kg) increased punished responding under the stimulus-shock termination and food schedules. The 5-HT2-selective receptor antagonist pirenperone (0.001-0.3 mg/kg) and the 5-HT2 receptor ligand spiperone (0.001-0.1 mg/kg) did not increase punished responding maintained by either event. In contrast, the prototype 5-HT2 ligand ketanserin increased punished responding maintained by food at doses (i.e., 0.1-3.0 mg/kg) that only decreased behavior maintained by stimulus-shock termination. Highly significant correlations were found between the peak rate-increasing effects of the 5-HT antagonists on punished responding maintained by stimulus-shock termination and their reported affinities at 5-HT1 (r = 0.99) and 5-HT2 (r = 0.95) binding sites. In contrast, under the food schedule a significant correlation was found only between the peak rate-increasing effects of the 5-HT antagonists and their reported affinities for the 5-HT1 site (r = 0.87). These findings confirm the involvement of serotonergic pathways in punishment-suppressed operant behavior and suggest that different populations of 5-HT receptors modulate punished behavior maintained by different types of consequent events (i.e., stimulus-shock termination or food).

Animals↗
PubMed1984

Reversal of the antinociceptive effects of centrally-administered morphine by the benzodiazepine receptor antagonist Ro 15-1788.

The effects of the benzodiazepine receptor antagonist, Ro 15-1788, were examined on analgesia induced by morphine after central (intracerebroventricular, i.c.v., or intrathecal, i.t.) and systemic administration. Analgesia was assessed in squirrel monkeys trained to respond under an electric shock titration procedure and in mice using the radiant heat tail-flick test. Central and systemic administration of morphine produced antinociceptive effects that were antagonized by 0.1 mg/kg of naloxone in both species. Ro 15-1788 antagonized the effects of morphine after central (i.c.v. or i.t.) administration but did not alter the effects of morphine given by the systemic route. This novel interaction suggests that Ro 15-1788 may be useful in pharmacologically separating neural substrates subserving opiate analgesia.

Animals↗
PubMed1984

Effects of thyrotropin-releasing hormone (TRH) and a TRH analogue, MK-771, on punished responding of squirrel monkeys.

The effects of thyrotropin-releasing hormone (TRH) and an enzyme-resistant analogue, MK-771, were compared on punished responding of squirrel monkeys maintained either by food presentation or stimulus-shock termination. Both TRH and MK-771 (1.0-30 mg/kg IM) produced dose-related decreases in punished responding maintained by food presentation and dose-related increases in punished responding maintained by shock termination. TRH was more potent than MK-771 in altering punished response rates maintained by either event.

Animals↗
PubMed1984

Ro 15-1788 and beta-CCE selectively eliminate diazepam-induced feeding in the rabbit.

Food intake was monitored in three female and one male adult rabbits following the administration of three drugs known to result in feeding increases in other species. The drugs, diazepam (1.0 mg/kg), cyproheptadine (0.03 mg/kg) and chlorpromazine (1.0 mg/kg) all produced large increases in food intake; of these, only the effect of diazepam, a benzodiazepine, was reversed by doses of the benzodiazepine antagonists Ro 15-1788 (0.3 mg/kg) and Ethyl beta-carboxylate (beta-CCE) (1.0 mg/kg) which, when given alone, did not affect feeding. The results support evidence suggesting that Ro 15-1788 and beta-CCE are specific antagonists of the benzodiazepine receptor and of their effects on a wide range of behaviors.

Animals↗
PubMed1983

Pharmacokinetic and pharmacodynamic factors contributing to the convulsant action of beta-carboline-3-carboxylic acid esters.

Both the methyl ester of beta-carboline-3-carboxylic acid and the 6,7-dimethoxy-4-ethyl derivative of this compound are potent convulsants in rodents, while the ethyl ester of beta-carboline-3-carboxylic acid does not cause convulsions, even when administered at very high doses. The rate of degradation of these compounds by rat plasma (in vitro) parallels their potencies as convulsants. In contrast, 3-carboethoxy-beta-carboline was found to potently elicit tonic and clonic convulsions in the squirrel monkey (Saimiri sciureus). Furthermore, the rate of degradation of 3-carboethoxy-beta-carboline in monkey plasma (in vitro) is negligible compared with rats. No significant differences were observed in either the potency or efficacy of GABA to inhibit [3H]beta-carboethoxy-beta-carboline binding in rat and monkey brain. These data strongly suggest that pharmacokinetic, as well as pharmacodynamic, factors may determine the pharmacologic profile of these beta-carboline-3-carboxylic acid esters.

Animals↗
PubMed1983

Drug history modifies the behavioral effects of pentobarbital.

Behavior of squirrel monkeys, maintained by the termination of stimuli associated with electric shock, was suppressed by response-dependent shock delivery. The effects of pentobarbital on this behavior depended on whether monkeys had previously received morphine. In monkeys without experience with drugs, pentobarbital increased responding. In monkeys with recent experience with morphine, however, pentobarbital resulted in a smaller increase or decrease in responding. The rate-decreasing effects of pentobarbital after a history of morphine administration could be reversed by the administration of d-amphetamine. These findings suggest that the behavioral effects of abused drugs may depend on previous experience with other drugs, even when those drugs are from a different pharmacological class.

Animals↗
PubMed1983

Prior behavioral experience can reverse the effects of morphine.

Morphine administration typically decreases responding of squirrel monkeys trained to avoid electric shock. However, the rate-decreasing effects of morphine on avoidance responding were reversed after either concurrent or prior exposure to a condition in which responding was maintained by shock presentation. These findings demonstrate that behavioral experience can play a significant role in determining the behavioral effects of drugs and that specific types of environmental conditions can completely reverse the usual effects those drugs have on behavior.

Animals↗
PubMed1983

Effects of cocaine, chlordiazepoxide, and chlorpromazine on responding of squirrel monkeys under second-order schedules of IM cocaine injection or food presentation.

Lever pressing by squirrel monkeys was maintained under second-order schedules of either food presentation or IM cocaine injection. Under one second-order schedule, every tenth response produced a brief (1-s) visual stimulus and the first brief stimulus presented after 30 min had elapsed was followed either by ten 300 mg food pellets or by a 3.0 mg IM injection of cocaine. Under another second-order schedule, the first response after 3 min produced the brief stimulus and the tenth brief stimulus was followed either by food or by cocaine. The two types of second-order schedules generated distinctly different patterns of responding. Furthermore, the temporal distribution of responding maintained by food presentation or cocaine injection sometimes differed slightly under the same schedule. Food presentation or cocaine injection occurred only at the end of each daily session, thereby allowing assessment of the effects of presession administration of cocaine, chlorpromazine (CPZ), and chlordiazepoxide (CDP) on responding at times when the direct effects of consequent cocaine injections were minimal or absent. Presession treatment with suitable doses of cocaine increased low rates of food- or cocaine-maintained responding under both types of second-order schedules, whereas CPZ only decreased responding. CDP increased responding in some monkeys, whereas in other monkeys it had little or no effect. Individual differences in the effects of CDP were not related to the schedule of reinforcement, the maintaining event, or the control rate of responding. Thus, the behavioral effects of cocaine, CDP, and CPZ were largely independent of whether responding was maintained by food or by cocaine.

Animals↗
PubMed1983

Comparison of the effects of antipsychotic drugs on the schedule-controlled behavior of squirrel monkeys and pigeons.

Lever pressing by squirrel monkeys and key pecking by pigeons were maintained under a multiple 3-min fixed-interval (FI), 30-response fixed-ratio (FR) schedule by the presentation of food. These responses, which differed under the two schedules, but were similar for both species, were used to compare the effects of antipsychotic compounds from different pharmacological classes. Except for differences in potency levels, the effects of intermediate doses of haloperidol and molindone were similar in monkeys and pigeons; these compounds decreased responding under the fixed-interval schedule at doses that did not affect fixed-ratio responding. Similar effects also occurred with chlorpromazine, promazine and thiothixene in pigeons. With monkeys, however, intermediate doses of promazine decreased fixed-ratio responding more than responding maintained under the fixed-interval schedule, while chlorpromazine and thiothixene produced similar effects on responding under both schedules. The effects of novel antipsychotic, clozapine, differed from those of the other agents in both monkeys and pigeons. With both species clozapine increased fixed interval responding at doses that did not affect responding under the fixed-ratio schedule. Doses required to reduce responding at least 50% were approximately 5 to 160 times greater for pigeons than for monkeys for all drugs except clozapine which was equipotent in both species. In monkeys the order of potency was haloperidol greater than molindone = thiothixene greater than chlorpromazine greater than clozapine greater than promazine, whereas in pigeons the order was haloperidol greater than thiothixene greater than clozapine greater than molindone greater than promazine greater than chlorpromazine.

Animals↗
PubMed1983

Effects of urinary pH on the behavioral responses of squirrel monkeys to nicotine.

The present study evaluated the behavioral effects of nicotine under conditions that manipulated urinary pH. The effects of nicotine were examined on the responding of squirrel monkeys under a multiple fixed-interval, fixed-ratio schedule of stimulus-shock termination when nicotine was administered alone or together with the gastric administration of an acidifier (ammonium chloride) or an alkalinizer (sodium bicarbonate). Responding under the FI schedule was increased markedly across a range of doses of nicotine (0.02-0.20 mg/kg). Responding under the FR was increased to a lesser extent by the lower doses of nicotine (0.02-0.05 mg/kg) and was decreased by doses of nicotine that increased responding under the FI (0.10-0.20 mg/kg). Generally, administration of the acidifier attenuated the effects of nicotine while administration of the alkalinizer potentiated those effects. These findings support the argument that changes in cigarette smoking under conditions that alter urinary pH involve nicotine per se. In addition, a new interpretation of the relationship between urinary pH and cigarette smoking is offered.

Ammonium Chloride↗
PubMed1983

Interrelationships between behavior and pharmacology as factors determining the effects of nicotine.

Behavioral consequences play an important role in determining subsequent behavior. The specific effects a particular consequent event will have, however, depend on many factors. Under certain conditions, the same event can produce diametrically opposite effects on behavior. Nicotine and electric shock are events which can function either as reinforcers capable of maintaining behavior, or as punishers which can suppress behavior. The reinforcing or punishing properties of consequent events depend on the prior experience of the organism and on the conditions existing at the time those events occur. The study of these pivotal events, and of those factors which contribute to their dual behavioral effects, has provided important information for developing a better understanding of general processes governing behavior. Further, the results of these studies have clarified the role of both behavioral and environmental factors in the initiation and maintenance of drug-taking behavior.

Animals↗
PubMed1983

Response suppression by visual stimuli paired with postsession d-amphetamine injections in the pigeon.

Responding of pigeons, maintained under a fixed-interval 3-minute schedule of food presentation, was decreased on days that the color of the lights illuminating the food magazine was changed and d-amphetamine (1.0 mg/kg, i.m.) was injected after the session. Responding was not decreased by keylight color changes paired with postsession d-amphetamine or by postsession injections of saline. Administration of pentobarbital (3.0 to 5.6 mg/kg), but not d-amphetamine (.3 to 3.0 mg/kg), before the session increased rates of responding suppressed by drug-paired magazine lights. Responding maintained under a fixed-ratio 30-response schedule was not decreased when differently colored magazine lights were paired with a low (.3 mg/kg) postsession dose of d-amphetamine; with high (3.0 mg/kg) postsession doses, however, responding was completely suppressed after two pairings. The effects of pairing magazine stimuli with an intermediate (1.0 mg/kg) postsession dose of d-amphetamine depended upon the magnitude of prior postsession doses. After being paired with a low dose, stimuli paired with 1.0 mg/kg did not suppress responding. After being paired with a high dose, stimuli paired with 1.0 mg/kg completely suppressed responding. The suppression of food-maintained responding by stimuli paired with postsession drug administration depends upon both behavioral and pharmacological variables.

Animals↗
PubMed1982

Short-term symptom change in outpatient psychiatric disorders.

Changes in symptomatology (Hopkins Symptom Checklist scales) during a three- to four-week period were observed in a group of subjects (symptomatic volunteers) who had specific psychiatric disorders (Research Diagnostic Criteria [RDC]) and who were not currently receiving or awaiting treatment. Four of the depressive disorder categories and two of the anxiety disorder categories showed a significant drop in the primary symptomatology. There was a differential effect of diagnosis on the amount of this "spontaneous" symptom reduction; for the HSCL scales depression and panic-phobic anxiety, the RDC disorders with the highest initial levels of those symptoms (major depressive disorder; panic anxiety disorder, combined panic-phobic anxiety disorder) showed the least reduction in that symptomatology.

Adult↗