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Target Concepts:
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Query: EC:3.4.16.2 (
PCP
)
3,761
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Place conditioning paradigms are widely used for determining the motivational properties of drugs. Phencyclidine (
PCP
) has been a common drug of abuse during the past two decades and has a rewarding effect in animals. However,
PCP
produces place aversion in the conditioned place preference (CPP) task in animals. Here, we report the possible neuronal mechanisms of
PCP
-induced place aversion and preference in the CPP task in rodents. In naive rats and mice,
PCP
dose-dependently produced place aversion and
PCP
had a significant effect at the doses of 4 and 8 mg/kg in rats and mice, respectively. The aversive effect of
PCP
(4 mg/kg) in rats was significantly attenuated by ritanserin (3 and 10 mg/kg), a serotonin 15-HT2) receptor antagonist whereas the lesion of serotonergic (5-HTergic) neurons by 5,7-dihydroxytryptamine (100 micrograms i.c.v.) and alpha-methyl-rho-tyrosine (AMPT; 100 mg/kg), a tyrosine hydroxylase inhibitor, did not affect the aversive effect of
PCP
. In rats pretreated with
PCP
(10 mg/kg/day) for 14 days, tolerance was developed to
PCP
(4 mg/kg)-induced place aversion. In rats and mice pretreated with
PCP
(10 mg/kg/day) for 28 days, however,
PCP
dose-dependently produced place preference but not aversion. The preferred effect of
PCP
(8 mg/kg) in mice preteated with
PCP
(10 mg/kg/day for 28 days) was significantly attenuated by AMPT (100 mg/kg) and 6-hydroxydopamine (100 micrograms i.c.v.) a dopaminergic (DAergic) neurotoxin, but not by
DSP-4
(30 mg/kg), a noradrenergic neurotoxin and ritanserin. In mice pretreated with methamphetamine (1 mg/kg/day) for 14 days,
PCP
(8 mg/kg) produced place preference. These findings suggest that 5-HTergic and DAergic systems are involved in the
PCP
-induced place aversion and preference, respectively, and some changes in the neuronal systems including DAergic systems, induced by repeated
PCP
treatment play a critical role in the addiction of
PCP
.
...
PMID:Neuronal mechanisms of phencyclidine-induced place aversion and preference in the conditioned place preference task. 981 6
We investigated the molecular mechanisms of development to phencyclidine (
PCP
)-induced rewarding effect by using tyrosine hydroxylase (TH) heterozygous (TH(+/-)) mice.
PCP
(8 mg/kg) induced the place preference in wild-type mice pretreated with
PCP
(10 mg/kg/day for 28 days). The place preference induced by
PCP
is attenuated by 6-hydroxydopamine, a dopaminergic neurotoxin, and (+) SCH-23390, a dopamine-D1 receptor antagonist, but not by
DSP-4
, a noradrenergic neurotoxin, and (-) sulpiride, a dopamine-D2 receptor antagonist. In TH(+/-) mice pretreated with
PCP
(10 mg/kg/day for 28 days), no
PCP
(8 mg/kg)-induced place preference was observed. In wild-type mice pretreated with
PCP
, the levels of cAMP, cAMP response element binding protein (CREB), and c-fos mRNA in the nucleus accumbens were increased. The levels of cAMP, CREB, and c-fos mRNA in the nucleus accumbens were not increased by the same treatment schedule of
PCP
in TH(+/-) mice. These findings suggest that changes in dopaminergic and/or cAMP signal cascades induced by repeated
PCP
treatment play an important role in the development of
PCP
-induced rewarding effect.
...
PMID:Involvement of signal transduction cascade via dopamine-D1 receptors in phencyclidine dependence. 1554 1
