Yukihiro Noda and Toshitaka Nabeshima*
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University
Graduate School of Medicine,
65 Tsuruma-cho, Showa-ku, Nagoya 466-8560, Japan
*ﾊTo whom correspondence should be addressed.
Abstract: Catecholaminergic and/or cyclic AMP (cAMP) systems
have been demonstrated to be involved in the development of drug dependence.
We investigated the involvement of both systems in psychological dependence
on phencyclidine (PCP) by using tyrosine hydroxylase (TH) heterozygous (TH+/-)
and cAMP response element binding protein (CREB) binding protein (CBP) heterozygous
(CBP+/-) mice. PCP (8ﾊmg/kg) induced place preference in wild-type
mice pretreated with PCP (10ﾊmg/kg once a day for 28ﾊdays). In these mice,
the level of cAMP in the striatum, but not in the thalamus, was increased
one day after the last injection of PCP (10ﾊmg/kg). In TH+/-
and CBP+/- mice pretreated with PCP (10ﾊmg/kg per day for 28ﾊdays),
however, no PCP (8ﾊmg/kg)-induced place preference was observed. The level
of cAMP in the striatum was increased in CBP+/- mice, but not
TH+/- mice. Furthermore, we have demonstrated that the place
preference induced by PCP is attenuated by 6-hydroxydopamine, a dopaminergic
neurotoxin, and (+)ﾊSCH-23390, a dopamine-D1 receptor antagonist, but not
by DSP-4, a noradrenergic neurotoxin, and (-)ﾊsulpiride, a dopamine-D2 receptor
antagonist. These findings suggest that catecholamines and CBP are involved
in the development of psychological dependence on PCP and that changes in
dopaminergic and/or cAMP systems induced by repeated PCP treatment play
an important role in the addiction to PCP.
Keywords: Phencyclidine, Psychological dependence, Catecholamine biosynthetic
pathway,
Dopamine-D1 receptor, Cyclic AMP pathway, Conditioned place preference