Involvement of extrapyramidal motor mechanisms in the suppression of locomotor activity by antipsychotic drugs: a comparison between the effects produced by pre- and post-synaptic inhibition of dopaminergic neurotransmission

Abstract

The effects of two proposed dopaminergic autoreceptor agonists, (-)3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP) and the azepine derivative B-HT 920, on spontaneous locomotor activity, treadmill locomotion, and catalepsy in the rat have been compared with the effects produced by the postsynaptic dopamine (DA) receptor blocking agent haloperidol. It was found that the threshold dose for suppression of exploratory locomotor activity was 0.5, 0.005 and 0.2 mg/kg for (-)3-PPP, B-HT 920 and haloperidol, respectively. The corresponding doses for suppression of treadmill locomotion were 8.0, 5.12 and 0.2 mg/kg, respectively. Furthermore, (-)3-PPP and B-HT 920, in contrast to haloperidol, did not produce any catalepsy. Thus, using exploratory locomotor activity as an index of limbic forebrain DA functions and treadmill locomotion and catalepsy as indices of extrapyramidal DA functions, the DA autoreceptor agonists, in contrast to the postsynaptic antagonist, show a difference in the doses required to produce these effects. The designation of the behavioral functions as "limbic" or extrapyramidal is supported by the finding that scopolamine, 0.8 mg/kg, antagonized the haloperidol-induced suppression (0.2 mg/kg) of treadmill locomotion, but not the suppression of exploratory locomotor activity.