Leonard Cook

BEHAVIORAL EFFECTS OF SOME PSYCHOPHARMACOLOGICAL AGENTS

Behavioral responses developed in rats have been employed in the evaluation of the comparative effects of several central nervous system (CNS) active pharmacological agents. Differentiation has been made between those CNS active materials that have a specific effect on a conditioned response (chlorpromazine, reserpine, morphine), and those that have a somewhat nonspecific effect on a conditioned response (barbital, pentobarbital, methylparafynol, meprobamate). The interrelationships between reserpine and serotonin in the CNS have been described by Pletscher et al.’ The effect of serotonin itself upon a conditioned response has also been examined in this study. Lysergic acid diethylamide (LSD) has been reported to antagonize certain properties of serotonin (Gaddum,2 Shore et ~ l . , ~ Costa4) and reserpine (Shore et ~ 1 . ~ ) . We have utilized the conditioned response to examine the interactions of lysergic acid diethylamide with reserpine and serotonin, as well as chlorpromazine, morphine, and meprobamate. Mescaline was also studied, in a manner similar to LSD-25, for possible interaction with conditioned-response blocking agents.

Ribonucleic Acid: Effect on Conditioned Behavior in Rats

Acquisition of a behavioral response motivated by shock was enhanced in rats chronically treated with yeast ribonucleic acid, and resistance to extinction was greater in rats so treated than in controls. This extends the role of ribonucleic acid to include a behavioral effect in laboratory mammals treated with a purified preparation from yeast.

Epinephrine, norepinephrine, and acetylcholine as conditioned stimuli for avoidance behavior.

Conditioned leg-flexion responses in dogs were developed with electric shock as an unconditioned stimulus and intestinal stimulation or the effects of injections of various drugs as conditioned stimuli. It is concluded that physiological effects can play a role in the development and maintenance of conditioned avoidance behavior.

Effects of combined treatment with trifluoperazine-HCl and amobarbital on punished behavior in rats

SummaryAmobarbital and certain low doses of trifluoperazine hydrochloride each attenuated the suppressant effects of punishment on response rates of rats in a multiple schedule of reinforcement containing punishment and non-punishment components. Combined treatment with these two agents, at a dose ratio of 1∶15 of trifluoperazine-HCl (base weight) to amobarbital, also attenuated the effects of punishment at all dose levels tested. The effect of the combined treatment was qualitatively similar to that seen following treatment with chlordiazepoxide. Combined treatment produced an effect on punished behavior at a dose level containing an ineffective dose of trifluoperazine-HCl and the degree of effect, at this dose level, was significantly greater than that produced by amobarbital alone, at this dose level. The effects of the combined treatment on non-punished responding were similar to those of trifluoperazine-HCl alone.In the procedure described, stable performance was established, and responding in both components of the schedule was maintained, for long periods of time without the necessity for repeated titration of shock intensities for individual rats. Increases as well as decreases of response rates in the punishment component could be measured with all rats following treatment with various pharmacological agents.

Some pharmacological observations on tranylcypromine (SKF trans-385), a potent inhibitor of monoamine oxidase.

Summary Treatment of rabbits with tranylcypromine followed by the injection of reserpine produces central nervous system stimulation and a marked rise in rectal temperature. The effects produced by tranylcypromine are assumed to reflect the activity of this agent as an inhibitor of monoamine oxidase.

Pharmacological effects of Ro 22-1319: A new antipsychotic agent

Ro 22-1319, a novel pyrroloisoquinoline compound, was identified as a potential antipsychotic agent in a rat discrete avoidance procedure that is highly specific for such agents. Results in this test are highly correlated with the clinical potency of all types of antipsychotic agents. The avoidance-blocking potency of Ro 22-1319 (0.7 mg/kg) in this procedure approached that of haloperidol (0.4 mg/kg) and was 7- and 12-times greater than that of chlorpromazine and clozapine, respectively. Ro 22-1319 exhibited similar high potency in other rat and monkey avoidance procedures, rat motor activity, and antagonism of apomorphine emesis in dogs. High potency and antipsychotic-like activity have been demonstrated in monkey EEG and in a in vivo 3H-spiroperidol binding assay. Although studies of amphetamine antagonism in rats indicate antidopaminergic activity at nigrostriatal sites, Ro 22-1319 exhibited relatively weaker cataleptogenic and antistereotypic activity than haloperidol, and had minimal activity in a rat chronic stereotypy model of receptor supersensitivity. This profile suggests that Ro 22-1319 is an efficacious antipsychotic compound, almost as potent as haloperidol, with fewer or less intense extrapyramidal effects and low potential for tardive dyskinesia.

Effect of repeated oral administration of monoamine oxidase inhibitors on rat brain amines.

Summary Repeated daily oral administrations of tranylcypromine (trans-2-phenyl-cyclopropylamine) (5 mg/kg, b.i.d.) or of iproniazid (1-isonicotinyl-2-isopropyl hydrazine) (50 and 100 mg/kg, b.i.d.) to male albino rats, Wistar strain, for periods of from 3 to 10 days resulted in cumulative increases in brain serotonin concentration of from 2 to 4 times that produced by a single administration of the drug. The increase in norepinephrine concentration was not appreciably different from that following a single administration of the drug. No significant or consistent effect upon the spontaneous motor activity of the rats was observed.

Yeast Ribonucleic Acid: Analysis of Effects on Pole-Climb Avoidance Behavior*

SummaryYeast RNA treatment increases rate of acquisition of pole-climb avoidance behavior in rats and prolongs retention of this behavior under extinction conditions. These effects of yeast RNA treatment appear to be primarily related to its interaction with components of the behavior which are present even before the emission of the first pole-climb response. Differences were also found between yeast RNA-treated rats and control rats in the relationship of performance during acquisition to performance under extinction conditions. These differences suggest that, in addition to its effects before the emission of the first pole-climb response, yeast RNA also interacts with behavior throughout the conditioning procedure.