TY - JOUR
T1 - The effect of phencyclidine on dopamine synthesis and metabolism in rat striatum
AU - Doherty, J. D.
AU - Simonovic, M.
AU - So, R.
AU - Meltzer, H. Y.
N1 - Funding Information:
We wish to express our appreciation to Dr. Sher-win Wilk of the Mt. Sinai School of Medicine for determining the DOPAC and HVA levels and to Dr. William Scott of Hoffman La Roche for a generous supply of Ro4-4602. Supported in part by USPHS DA 02081 and MH 30,938 and by the Department of Mental Health, State of Illinois. HYM is recipient of RCSA HM 47,808. MS is a recipient of PSH MH 14,274.
PY - 1980
Y1 - 1980
N2 - Previous behavioral and neurochemical studies indicate that phenyclidine (PCP), a potent psychotomimetic agent, interacts with central dopaminergic systems. We have examined the effects of PCP on the rate of accumulation of 3,4-dihydroxyphenylalanine (DOPA) after the inhibition of L-aromatic amino acid decarboxylase and on the levels of dopamine (DA) metabolites: 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in rat striatum. PCP, in doses from 2.5 to 50 mg/kg, decreased the rate of striatal DOPA accumulation. PCP did not antagonize the increase in the rate of striatal DOPA formation caused by haloperidol, reserpine or γ-butyrolactone (GBL). When given alone, PCP decreased striatal levels of DOPAC and HVA, while it greatly potentiated the haloperidol-induced rise in striatal levels of these two metabolites. PCP is considerably less effective than d-amphetamine in promoting the release of 3H-DA from preloaded striatal slices in vitro. Our results are consistent with the interpretation that PCP potentiates the synaptic effects of endogenous DA. Its mechanism of action appears to be closely related to that of a category of drugs known as non-amphetamine stimulants, which, among others, includes methylphenidate, amfonelic acid and cocaine.
AB - Previous behavioral and neurochemical studies indicate that phenyclidine (PCP), a potent psychotomimetic agent, interacts with central dopaminergic systems. We have examined the effects of PCP on the rate of accumulation of 3,4-dihydroxyphenylalanine (DOPA) after the inhibition of L-aromatic amino acid decarboxylase and on the levels of dopamine (DA) metabolites: 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in rat striatum. PCP, in doses from 2.5 to 50 mg/kg, decreased the rate of striatal DOPA accumulation. PCP did not antagonize the increase in the rate of striatal DOPA formation caused by haloperidol, reserpine or γ-butyrolactone (GBL). When given alone, PCP decreased striatal levels of DOPAC and HVA, while it greatly potentiated the haloperidol-induced rise in striatal levels of these two metabolites. PCP is considerably less effective than d-amphetamine in promoting the release of 3H-DA from preloaded striatal slices in vitro. Our results are consistent with the interpretation that PCP potentiates the synaptic effects of endogenous DA. Its mechanism of action appears to be closely related to that of a category of drugs known as non-amphetamine stimulants, which, among others, includes methylphenidate, amfonelic acid and cocaine.
KW - Dopamine agonist
KW - Phencyclidine
KW - Reuptake blocker
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U2 - 10.1016/0014-2999(80)90386-6
DO - 10.1016/0014-2999(80)90386-6
M3 - Article
C2 - 7398783
AN - SCOPUS:0018874892
SN - 0014-2999
VL - 65
SP - 139
EP - 149
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2-3
ER -