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Description:
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Based on anatomical studies demonstrating a serotonergic (5 -HT ) innervation to the deep cerebeUar nudei (DCN ) and autoradiographic study that identified at least three 5 -HT receptor subtypes in the DCN , the present electrophysiological studies utilizing an in -vitro cerebellar slice preparation were designed to address three major objectives : (1 ) the actions of 5 -HT or neurons of the dentate /interpositus nudei , (2 ) the receptor subtypes responsible for mediating effects of 5 -HT , and (3 ) the potential role of adenylate cydase as a transducer of inhibitory effects of 5 -HT .
Superfusion and iontophoretic appUcation of 5 -HT caused either exdtation or inhibition of the spontaneous activity of dentate /interpositus neurons . Studies utilizing selective agonists and antagonists for 5 -HT receptor subtypes revealed that the 5 -HTiA receptor subtype is responsible part , for mediating 5 -HT -induced inhibition . In addition , the 5 -HT2 receptor subtype elicits indirect inhibition presumably by activation of GABAergic intemeurons . These studies also demonstrated that the 5 -HT4 receptor subtype is responsible for mediating exitatory and inhibitory effects of 5 -H
Data from experiments utilizing compounds that affect the adenylate cyclase second messenger cascade at various stages indicated that these receptor subtyp >es are potentiaUy negatively coupled to adenylate cydase . Sp )ecificaUy , inhibitory effects eUdted by activation of 5 -HTi A and 5 -HT4 receptor subtypes mediate inhibition possibly via a decrease in activity of s - adenylate cydase -dependent system in these neurons . |