PubMed Health⌕ Search

Biomedical subjects

R D Sturgeon

Publications and source records attributed to R D Sturgeon.

10 recordsLinked to original sources

Behavioral effects of chronic phencyclidine administration in rats.

The development of tolerance to phencyclidine (PCP) was examined in rats using behavioral rating scales with simultaneous measurements of locomotor activity, stereotyped behaviors, and ataxia. Significant tolerance to the stereotyped behaviors and ataxia induced by 5 or 10 mg/kg PCP was found on day 5 of chronic drug treatment. Because ataxia interferes with PCP-induced locomotor activity (Sturgeon et al. 1979), tolerance to PCP-induced ataxia produced an increase in locomotor activity on day 5. Tolerance to the ataxia, but not to the stereotyped behaviors induced by PCP, was more prominent after day 15 of PCP administration than after day 5. Administration of PCP for 15 days resulted in significant decrease in locomotor activity for the 5 mg/kg group but not for the 10 mg/kg group. These results suggest that behavioral tolerance, rather than supersensitivity, develops after chronic PCP administration. The effects of PCP returned to baseline over a 14-day withdrawal period for rats treated with 5 mg/kg PCP for 15 days. Rats treated with 10 mg/kg PCP for 15 days still had not returned to baseline when tested 28 days after cessation of PCP treatment.

Animals↗

Effects of lithium on behaviour induced by phencyclidine and amphetamine in rats.

d-Amphetamine and phencyclidine (PCP) have both been reported to produce manic-like sequela in humans, effects that are reportedly antagonized by lithium. To test the hypothesis that the acute effects of these drugs in rats may serve as models of mania, the behaviors induced by d-amphetamine (3 mg/kg) or PCP (5 mg/kg) were quantified on behavioral rating scales subsequent to chronic dietary pretreatment with lithium carbonate or control diet. On day 14 of pretreatment, PCP-induced stereotyped behaviors and ataxia were potentiated in rats receiving lithium (plasma levels 1.0 +/- 0.23 mEq/l). PCP-induced locomotor activity was not affected by lithium pretreatment. Stereotypies and locomotion induced by d-amphetamine were also not significantly affected by lithium pretreatment. These results suggest that neither PCP nor amphetamine administered acutely to rats will be useful models to explore the manic-like symptoms produced by these drugs in humans.

Animals↗

A comparison of the effects of neuroleptics on phencyclidine-induced behaviors in the rat.

The dose-response effects of neuroleptic pretreatment on phencyclidine (PCP; 3 or 5 mg/kg)-induced locomotor activity, stereotyped behaviors and ataxia were quantified in groups of male rats using rating scales recently developed in this laboratory. Three butyrophenone neuroleptics consistently produced dose-dependent antagonism of the behavioral effects of PCP administration. Fluphenazine antagonized the behavioral effects produced by 3 mg/kg PCP but not those produced by 5 mg/kg PCP. Each of the other neuroleptics examined (chlorpromazine, thioridazine, mesoridazine, triflupromazine, cis-flupenthixol) had no consistent antagonistic effect or actually enhanced one or more of the behavioral effects of PCP. Some neuroleptics slightly reduced PCP locomotion or stereotypies at high doses, but these effects were probably a non-specific consequence of the synergistic ataxia-producing properties of these drugs. In a second set of experiments, atropine sulfate pretreatment increased PCP-induced locomotor activity and stereotyped behaviors but had no effect on ataxia; pretreatment with physostigmine produced opposite effects. Combined pretreatment with haloperidol and atropine sulfate significantly reduced only haloperidol antagonism of PCP-induced ataxia, thus suggesting that non-dopoaminergic effects of neuroleptics may interfere with their ability to antagonize PCP.

Animals↗

Effect of antidepressants, lithium and electroconvulsive treatment on rat serum prolactin levels.

The ability of antidepressant drugs, electroconvulsive treatment (ECT), or lithium chloride (LiCl), to modify prolactin secretion in the rat was studied. Chlorimipramine, citalopram, fluoxetine, imipramine and zimelidine potentiated the low dose 5-hydroxytryptophan (5-HTP)-induced increase in prolactin secretion, suggesting inhibition of serotonin (5-HT) uptake by these drugs. Amitriptyline, doxepin, iprindole, mianserin and trazadone inhibited the prolactin stimulating effects of high doses of 5-HTP and quipazine, suggesting that these drugs have 5-HT receptor blocking properties. Tandamine inhibited only 5-HTP-induced increase in prolactin secretion. Chronic administration of imipramine, potentiated the effect of low dose 5-HTP significantly more than an acute dose. Amitriptyline, produced similar inhibition of the 5-HTP-induced increase in prolactin secretion after both acute and chronic administration. The ability of bupropion and mazindol to inhibit alpha-methylparatyrosine-induced prolactin secretion, and of nomifensine to inhibit reserpine-induced prolactin secretion, is consistent with other evidence that these agents are indirect dopamine (DA) agonists. Desipramine, acutely, had no effect on any of the above paradigms but after chronic administration, potentiated the effect of low dose 5-HTP on prolactin secretion. Nortriptyline had no effect on prolactin secretion after acute or chronic treatment. ECT for 10 days did not affect the ability of a 5-HT agonist or d-amphetamine to modify prolactin secretion. However, chronic, but not acute, treatment with LiCl markedly enhanced the prolactin response to 5-HT agonists and reserpine while shifting the dose response curve for d-amphetamine and apomorphine to the right. These results are discussed in light of current theories of the role of 5-HT and DA in depression.

5-Hydroxytryptophan↗

Effects of phencyclidine and methylphenidate on d-amphetamine-induced behaviors in reserpine pretreated rats.

The effects and interactions of phencyclidine (PCP), methylphenidate and d-amphetamine on locomotor activity, stereotyped behavior and ataxia in reserpine- and vehicle-pretreated rats were examined. The behaviors of rats receiving PCP alone or in combination with other drugs were quantified along three dimensions (locomotor activity, stereotyped behavior, and ataxia) on scales developed in this laboratory. The behaviors of groups receiving methylphenidate and/or d-amphetamine in treatment combinations other than those including PCP were quantified using a well known d-amphetamine behavioral rating scale. PCP, methylphenidate and d-amphetamine each induced significant increases in locomotor activity and stereotyped behavior when administered alone. Reserpine was found to antagonize PCP-induced locomotor activity and stereotyped behavior, and methylphenidate-induced stereotyped behavior at a dose which either potentiated or had no significant effect upon d-amphetamine-induced behavior (depending upon the scale used). Reserpine also potentiated PCP-induced ataxia. Whereas PCP potentiated the locomotor activity induced by d-amphetamine in both reserpine- and vehicle-pretreated subjects, methylphenidate marginally antagonized d-amphetamine-induced stereotypy in reserpine-pretreated subjects. PCP-induced ataxia in reserpine pretreated subjects appeared moderately reduced in subjects also receiving d-amphetamine. In general, the behavioral effects of PCP appear to be more similar to those of methylphenidate than to those of d-amphetamine, but differences are also found between PCP and methylphenidate. The results are discussed in relation to a behavioral model recently proposed as a method for differentiating indirect dopamine agonists on the basis of their neurochemical mechanisms of action.

Animals↗

Behavioral rating scales for assessing phencyclidine-induced locomotor activity, stereotyped behavior and ataxia in rats.

Behavioral rating scales were developed for quantification of phencyclidine (PCP)-induced locomotor activity, stereotyped behavior and ataxia in rats. The dose-response relationship for PCP-induced locomotor activity was found to be an inverted U-shaped function over the first 25 min after injection while over the last 30 min of the experiment the function was highly linear. A linear dose-response relationship was found for ratings of stereotyped behavior and ataxia throughout the 90 min period of observation. The ratings of these two behaviors were found to be closely parallel. The effects of PCP on locomotor activity were found to be greatest during those intervals when stereotyped behavior and ataxia were at moderate levels. Ratings of locomotor activity may be confounded by ataxia when PCP is administered alone or in combination with other drugs.

Animals↗