ELECTRO-PHYSIOLOGICAL EVIDENCE FOR PRESYNAPTIC ACTIONS OF PHENCYCLIDINE ON NORADRENERGIC TRANSMISSION IN RAT CEREBELLUM

  • 1 January 1980
    • journal article
    • research article
    • Vol. 215  (3) , 606-613
Abstract
The actions of the psychotomimetic drug phencyclidine (PCP), a drug widely abused by humans, were studied using Purkinje neurons in the cerebellum of urethane-anesthetized rats. PCP, applied by micropressure ejection through multibarreled micropipettes, depressed the spontaneous activity of these neurons as recorded by extracellular electrophysiological techniques. This depressant effect was blocked by neuroleptic drugs (fluphenazine, haloperidol, flupenthixol) and Li, both of which block the depressant effects of norepinephrine but not those of GABA. PCP-elicited depressions could not be obtained in rats in which the cerebellar noradrenergic terminals were lesioned selectively by pretreatment with the neurotoxin 6-hydroxydopamine. PCP was still an effective depressant in animals after destruction of non-noradrenergic intrinsic excitatory and inhibitory interneurons which synapse on the Purkinje cell by neonatal X-irradiation. Further treatment of the X-irradiated animal with 6-hydroxydopamine resulted in Purkinje neurons which were not responsive to PCP. Administration of magnesium ions, which reduces the release of neurotransmitters from afferent terminals, blocked the depressant effects of PCP. Apparently PCP acts in the cerebellum by a presynaptic mechanism involving the release of norepinephrine from intact, functioning noradrenergic terminals.

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