Electrophysiological effects of phencyclidine and the sigma agonist ditolylguanidine in the cerebellum of the rat.
The electrophysiological actions of phencyclidine (PCP) and the sigma agonist 1,3-di(2tolyl)guanidine (DTG) were examined in the cerebellum of urethane-anesthetized rats. The object of the study was to determine if PCP and sigma agonists shared a common mechanism of action. The cerebellar Purkinje neuron was chosen because it has sigma receptors but not N-methyl-D-aspartate receptors, where PCP has additional effects. Both DTG and PCP decreased the spontaneous discharge rate of cerebellar Purkinje neurons after parenteral administration. When the drugs were applied locally to single Purkinje neurons, using pressure ejection through multibarrel micropipettes, both compounds decreased the spontaneous activity of the neurons with equal potency. Previous studies have shown that the actions of PCP in the cerebellum are dependent upon an interaction with noradrenergic terminals from the nucleus locus coeruleus. A similar finding was made in this study for DTG. Elimination of the noradrenergic input by lesion with the neurotoxin, 6-hydroxydopamine, diminished equally the effects of PCP and DTG. Treatment of the animals with haloperidol had similar effects. It is concluded that PCP and the sigma agonist DTG both act as indirect noradrenergic agonists in the cerebellum.
Kim
M
M
Denver Veterans Administration Medical Center, CO 80776.
Bickford
P C
PC
D000818:Animals; D002531:Cerebellum / Q000187:drug effects*; D004594:Electrophysiology; D006146:Guanidines / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000502:physiology; D016627:Oxidopamine / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D009435:Synaptic Transmission / Q000187:drug effects
D006146:Guanidines; D016627:Oxidopamine; D010622:Phencyclidine; D006220:Haloperidol; C050232:1,3-ditolylguanidine; D009638:Norepinephrine