Low doses of apomorphine elicit two opposing influences on dopamine cell electrophysiology.
Dopamine (DA) cells are known to be very sensitive to direct acting DA agonists, and inhibition of DA cell firing by low doses of DA agonists is generally considered to be an action of these agonists on DA cell autoreceptors. During intracellular recording from spontaneously discharging DA cells in vivo, intravenous administration of apomorphine (20 micrograms/kg i.v.) elicited a hyperpolarization and an increase in input resistance. The calculated reversal potential of the apomorphine effect was approximately -40 mV. However, in non-firing DA cells the reversal potential of these effects was significantly different (P less than 0.01), being close to the reversal potential of responses induced by stimulation of striatonigral pathways (i.e. -67 mV). In addition, haloperidol (0.01 mg/kg i.v.) reversed the hyperpolarization produced by apomorphine but not the increase in input resistance. Transection of striatonigral pathways eliminated most of the increase in input resistance accompanying apomorphine administration, and shifted the apomorphine reversal potential to a value positive to 0 mV. Low doses of apomorphine were also found to affect a class of zona reticulata (ZR) interneurons. Apomorphine caused decreases in ZR cell firing rate, which were abolished by striatonigral pathway transection. Thus, the following mechanism is proposed for the electrophysiological actions of autoreceptor-selective doses of apomorphine on DA cells: (1) apomorphine directly inhibits spontaneous DA cell discharge by inhibiting the slow depolarization preceding action potentials and thereby hyperpolarizes the DA cell, (2) decreased DA cell firing disinhibits GABAergic striatal cells, whose increased firing preferentially (3) inhibits GABAergic ZR interneurons, and thus (4) removes an inhibitory input to DA cells, resulting in an increase in input resistance.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000502:physiology*; D004553:Electric Conductivity; D006220:Haloperidol / Q000494:pharmacology; D007395:Interneurons / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009434:Neural Pathways / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013378:Substantia Nigra / Q000187:drug effects*
D011954:Receptors, Dopamine; D006220:Haloperidol; D001058:Apomorphine; D004298:Dopamine