Interaction of benztropine and haloperidol actions on rat substantia nigra dopamine cell electrophysiological activity in vivo.
Despite the known efficacy of antimuscarinic agents in treating dopamine-related movement disorders, their effects on dopamine cell activity have not been well studied. We investigated the effects of systemically administered benztropine, an antimuscarinic agent that also inhibits the dopamine transporter, on substantia nigra dopamine neuron electrophysiological activity. Benztropine caused a dose-dependent inhibition of the firing rate of dopamine neurons in control rats but exerted baseline-dependent changes in burst firing. In rats pre-treated with haloperidol, which prevents the effects of dopamine transporter inhibitors on dopamine cell activity, benztropine either increased or decreased firing rate; however, it consistently increased burst firing. Thus, the antimuscarinic and psychostimulant properties of benztropine have differential effects on dopamine neuron firing rate and burst firing. The increase in burst firing seen in the presence of haloperidol may mediate some of the therapeutic effects of benztropine in the treatment of antipsychotic drug-induced movement disorders.
Todd
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Department of Neuroscience, Center for Neuroscience, University of Pittsburgh, PA 15260, USA. todd@neurosci.bns.pitt.edu
Grace
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AA
D000818:Animals; D001590:Benztropine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004594:Electrophysiology; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
D018492:Dopamine Antagonists; D018727:Muscarinic Antagonists; D001590:Benztropine; D006220:Haloperidol