Effect of 1-(m-chlorophenyl)piperazine and 1-(m-trifluoromethylphenyl)piperazine on locomotor activity.
The piperazine-type 5-hydroxytryptamine (5-HT) agonists 1-(m-trifluoromethylphenyl)piperazine (TFMPP), 1-(m-chlorophenyl)-piperazine (m-CPP), 1-(p-chlorophenyl)piperazine (p-CPP) and MK-212 [6-chloro-2-(1-piperazinyl)pyrazine], produced a dose-dependent suppression of spontaneous ambulatory behavior in rats. Pretreatment with the 5-HT antagonists metergoline, methysergide or mianserin, but not selective 5-HT2 or catecholamine antagonists, blocked the reduction of activity caused by TFMPP suggesting that the stimulation of 5-HT receptors was involved in causing this behavioral effect. Other behavioral signs of 5-HT receptor stimulation, such as the 5-HT behavioral syndrome or head-shaking behavior, were not observed in rats injected with TFMPP, m-CPP or MK-212 except at toxic doses. The ability of piperazine agonists to reduce locomotor activity in rats was altered by long-term changes in 5-HT neurotransmission. The destruction of 5-HT neurons by i.v.t. injection of the neurotoxin 5,7-dihydroxytryptamine potentiated the ability of m-CPP to inhibit ambulatory behavior. On the other hand, elevating 5-HT content by administering the monoamine oxidase inhibitors phenelzine or nialamide for 7 days reduced the ability of m-CPP to suppress locomotor activity. Acute administration of the monoamine oxidase inhibitors, or chronic administration of other antidepressants such as desmethylimipramine or iprindole, failed to alter m-CPPs activity-suppressant effects. These studies suggest that chronic changes in 5-HT neurotransmission produce compensatory changes which alter the behavioral response to these piperazine agonists. Taken together with other evidence that both TFMPP and m-CPP are agonists at 5-HT1B and 5-HT1C receptors, the effects of TFMPP and m-CPP on locomotor activity may be associated with the selective activation of 5-HT1C, or possibly 5-HT1B, receptors.
Lucki
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I
Department of Psychiatry, University of Pennsylvania, Philadelphia.
Ward
H R
HR
Frazer
A
A
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D011719:Pyrazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects
D000928:Antidepressive Agents; D008996:Monoamine Oxidase Inhibitors; D010879:Piperazines; D011719:Pyrazines; D011985:Receptors, Serotonin; C018406:1-(3-trifluoromethylphenyl)piperazine; C014896:6-chloro-2-(1-piperazinyl)pyrazine; C015068:1-(3-chlorophenyl)piperazine