TY - JOUR
T1 - Presynaptic dopaminergic activity of phencyclidine in rat caudate
AU - Johnson, S. W.
AU - Haroldsen, P. E.
AU - Hoffer, B. J.
AU - Freedman, R.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1984
Y1 - 1984
N2 - This study tested the hypothesis that phencyclidine (PCP) is an indirect dopamine (DA) agonist in the caudate nucleus. Single caudate neurons in rats anesthetized with urethane were recorded extracellularly with multibarrel micropipettes. Effects of drug solutions, applied by pressure microejection, were measured as changes in spontaneous and evoked neuronal activity. Caudate neurons were classified according to their latency-to-discharge in response to supramaximal cortical stimulation. PCP inhibited the spontaneous activity of 92% of neurons with latencies < 13 msec, while DA inhibited 87%. Both drugs inhibited evoked activity significantly less than spontaneous activity (P < .01). Neurons with latencies > 13 msec were excited by DA significantly more often (45%) than by PCP (13%; P < .05). Receptor stereospecificity is suggested by the finding that the (+)-isomer of the 3-methyl piperidine derivative of PCP was significantly more potent than the (-)-isomer for inhibition of spontaneous activity. Mg++, which blocks presynaptic release of neurotransmitter, significantly antagonized inhibitory effects of PCP on spontaneous activity, which suggests a presynaptic effect of PCP. DA, which acts postsynaptically, was much less affected by Mg++. The potency of PCP was significantly less in rats treated with reserpine or 6-hydroxydopamine than in control rats, suggesting the endogenous DA is required for the action of PCP. Fluphenazine and (+)-butaclamol, potent DA-receptor antagonists, blocked the effect of PCP, but (-)-butaclamol did not. These results support the hypothesis that PCP facilitates release and/or inhibits reuptake of DA in nerve terminals and thereby acts as an indirect DA agonist in the caudate. However, there may be a subpopulation of caudate neurons in which PCP acts by a nondopaminergic mechanism.
AB - This study tested the hypothesis that phencyclidine (PCP) is an indirect dopamine (DA) agonist in the caudate nucleus. Single caudate neurons in rats anesthetized with urethane were recorded extracellularly with multibarrel micropipettes. Effects of drug solutions, applied by pressure microejection, were measured as changes in spontaneous and evoked neuronal activity. Caudate neurons were classified according to their latency-to-discharge in response to supramaximal cortical stimulation. PCP inhibited the spontaneous activity of 92% of neurons with latencies < 13 msec, while DA inhibited 87%. Both drugs inhibited evoked activity significantly less than spontaneous activity (P < .01). Neurons with latencies > 13 msec were excited by DA significantly more often (45%) than by PCP (13%; P < .05). Receptor stereospecificity is suggested by the finding that the (+)-isomer of the 3-methyl piperidine derivative of PCP was significantly more potent than the (-)-isomer for inhibition of spontaneous activity. Mg++, which blocks presynaptic release of neurotransmitter, significantly antagonized inhibitory effects of PCP on spontaneous activity, which suggests a presynaptic effect of PCP. DA, which acts postsynaptically, was much less affected by Mg++. The potency of PCP was significantly less in rats treated with reserpine or 6-hydroxydopamine than in control rats, suggesting the endogenous DA is required for the action of PCP. Fluphenazine and (+)-butaclamol, potent DA-receptor antagonists, blocked the effect of PCP, but (-)-butaclamol did not. These results support the hypothesis that PCP facilitates release and/or inhibits reuptake of DA in nerve terminals and thereby acts as an indirect DA agonist in the caudate. However, there may be a subpopulation of caudate neurons in which PCP acts by a nondopaminergic mechanism.
UR - http://www.scopus.com/inward/record.url?scp=0021242742&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0021242742&partnerID=8YFLogxK
M3 - Article
C2 - 6707946
AN - SCOPUS:0021242742
SN - 0022-3565
VL - 229
SP - 322
EP - 332
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 1
ER -