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The effect of p-chloroamphetamine on motility in rats after inhibition of monoamine synthesis, storage, uptake and receptor interaction

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Abstract

The effect of PCA on motility was investigated after s.c. injection to rats in a familiar cage. The doses 1, 2, 5 and 10 mg/kg induced increasing hypermotility. PCA 1 and 2 mg/kg produced various normal behavioral items, but 5 and 10 mg/kg induced mainly abnormal jerky locomotion and head movements.

The effect of PCA 5 mg/kg was investigated in rats treated s.c. with various drugs affecting central monoamines. Pretreatment with the 5HT-synthesis inhibitor H 69/17 200 mg/kg, the tyrosinehydroxylase inhibitor H 44/68 250 mg/kg twice and reserpine 7.5 mg/kg inhibited PCA-hyperactivity. H 44/68 250 mg/kg once and the dopamine Β-hydroxylase inhibitor FLA 63 did not influence the effect of PCA.

Simultaneous administration of imipramine 3.1 mg/kg, chlorimipramine 0.9 mg/kg, desipramine 26 mg/kg, amitriptyline 15 mg/kg, doxepine 1.8 mg/kg, chlorpromazine 0.1 mg/kg, haloperidol 0.01 mg/kg, spiramide 0.01 mg/kg and chlorpheniramine 3.9 mg/kg antagonized PCA-hypermotility. Protriptyline 50 mg/kg, clozapine 20 mg/kg and benztropine 10 mg/kg showed no PCA-antagonism.

These results indicate that 5HT and DA release are involved in PCA-hyperactivity and that 5HT-membrane blockers inhibit uptake of PCA into brain 5HT neurons thus preventing 5HT release.

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  1. Department of Pharmacology, A/S Ferrosan, 2860, Soeborg, Denmark

    J. Buus Lassen

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Lassen, J.B. The effect of p-chloroamphetamine on motility in rats after inhibition of monoamine synthesis, storage, uptake and receptor interaction. Psychopharmacologia 34, 243–254 (1974). https://doi.org/10.1007/BF00421965

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