A role for electrotonic coupling in the striatum in the expression of dopamine receptor-mediated stereotypies.
Stimulation of dopamine (DA) receptors in the striatum evokes a number of alterations in motor behavior in rats, as well as causing several alterations in cellular physiology, including changes in membrane potential, cell excitability, afferent drive, and electrotonic coupling. One cellular property that is potently modulated by DA stimulation is electrotonic coupling, a process shown to subserve motor pattern generation. To examine whether electrotonic coupling plays a role in mediating a specific set of DA receptor-mediated motor behaviors, we tested the effects of two inhibitors of gap junction conductance, carbenoxolone (CARB) and anandamide (AEA), on apomorphine (APO)-induced motor responses. We then used intra-striatal infusions of CARB to determine the role of electrotonic coupling specifically in the ventral striatum in the expression of APO-induced behaviors. APO (2.5-3.0 mg/kg, i.p.) significantly increased motor activity (a composite score) and the frequencies of oral and sniffing stereotypies. APO also disrupted grooming initiation and completion. APO-induced oral stereotypies were selectively blocked by systemic administration of CARB (7.0, 35.0 mg/kg). Moreover, although CARB alone disrupted the initiation and completion of grooming sequences, it also partially normalized APO-induced disruptions in grooming. AEA (0.5, 1.5 mg/kg) also blocked APO-induced oral stereotypies at the higher dose, but differed from CARB in that it did not restore normal grooming behaviors but, instead, appeared to "release" locomotion. Bilateral infusion of carbenoxolone (50 pmol) into the ventral striatum also blocked the oral stereotypies induced by systemic APO. We conclude from these and previous experiments that gap junctions play an important role in normal motor behavior, and furthermore that disruption of motor behavior in the form of oral and sniffing stereotypies associated with systemic APO administration may be a consequence of this heightened electrotonic coupling in the striatum. These results may be relevant to diseases and pharmacotherapies associated with disruptions of motor and possibly cognitive sequencing.
Moore
Holly
H
Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Grace
Anthony A
AA
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002229:Carbenoxolone / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000502:physiology*; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology*
D011954:Receptors, Dopamine; D002229:Carbenoxolone; D001058:Apomorphine