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Efficacy of neuroleptics and antidepressants in the test of apomorphine hypothermia and some data concerning neurochemical mechanisms of the test

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Abstract

The action of 19 imipraminelike antidepressants (IAD) and related compounds and of 13 neuroleptics on the hypothermic effect of apomorphine (AP, 5 mg/kg i.p.) was investigated in mice (the test of AP hypothermia-APH). The strong specific neuroleptics such as trifluperidol, trifluperazine, and thioproperazine counteracted APH in doses from 0.006 mg/kg, whereas IAD counteracted APH in doses from 0.25 mg/kg (desmethylimipramine and melitracene). Among neuroleptics there is a good correlation between efficacy in the test of APH and efficacy in the tests of AP and amphetamine stereotypes, which reveal the central antidopamine action of neuroleptics. Among IAD there is a correlation between efficacy in the test of APH and the adrenopositive activity. Barbital Na, amobarbital, and pentobarbital reliably counteract APH in doses from 20 mg/kg. Amphetaminelike stimulants are effective in doses of about 1 mg/kg. Addition of scopolamine or adrenolytics does not essentially change the action of neuroleptics on APH. APH is probably the most universal simple test for the initial screening of potentially psychotropic drugs. Some previous results of the pharmacological analysis of APH are presented, which reveal the central link of APH and the central component of antagonizing APH by IAD. The hypothesis is proposed that the initial excitation of the central dopamine receptor by AP leads to the activation of the noradrenergic neuron, which is the subsequent link in producing APH.

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  1. Laboratory of Psychopharmacology, Bechterev Psychoneurological Research Institute, 193019, Leningrad, USSR

    E. L. Schelkunov

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Schelkunov, E.L. Efficacy of neuroleptics and antidepressants in the test of apomorphine hypothermia and some data concerning neurochemical mechanisms of the test. Psychopharmacology 55, 87–95 (1977). https://doi.org/10.1007/BF00432822

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  • DOI: https://doi.org/10.1007/BF00432822

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