Facilitation of GABA-induced depression with PCP and sigma receptor agonists was mediated through catecholaminergic pathways.
The purpose of this experiment was to investigate the interactions of norepinephrine with PCP (phencyclidine) and sigma receptor agonists--modulated GABA (gamma aminobutyric acid) response in the cerebellum. Drugs were directly applied to a single cerebellar Purkinje neuron of urethane-anesthesitized rat through a multibarrel pipette. (+)PCMP [1-(-1-phenylcyclohexyl)-3-methyl piperidine], a PCP receptor agonist, and dexoxadrol, a sigma receptor agonist, significantly enhanced GABA induced inhibition. In norepinephrine-depleted animals, however, both (+)PCMP and dexoxadrol did not modulate GABA's effect. In conclusion, our findings indicated that the PCP/sigma-induced facilitation of GABA reactions were mediated through noradrenergic system in the cerebellum.
Wang
Y
Y
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Kao
M C
MC
Lee
H K
HK
D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000502:physiology*; D004148:Dioxolanes / Q000494:pharmacology; D004594:Electrophysiology; D008297:Male; D009638:Norepinephrine / Q000502:physiology*; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017480:Receptors, sigma; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D004148:Dioxolanes; D010880:Piperidines; D011957:Receptors, Opioid; D017480:Receptors, sigma; C036590:1-(1-phenylcyclohexyl)-3-methylpiperidine; C005840:dioxadrol; D005680:gamma-Aminobutyric Acid; D010622:Phencyclidine; C579650:dexoxadrol; D009638:Norepinephrine