I  U  P  A  C

News & Notices

Organizations & People

Standing Committees




..Macro. Symp.

..Solubility Data



Links of Interest

Search the Site

Home Page


Pure Appl. Chem. Vol. 72, No. 6, pp. 1035-1044, 2000

Role of catecholamines and cyclic AMP systems in phencyclidine and morphine dependence. Study of mutant mice*

Toshitaka Nabeshima**, Takayoshi Mamiya, and Yukihiro Noda

Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, 65, Tsuruma-cho, Showa-ku, Nagoya 466-8560, Japan

Abstract: To investigate an involvement of catecholamines and/or the cyclic adenosine monophosphate (cAMP) systems in the development of drug dependence, we examined whether phencyclidine (PCP) and morphine dependence were developed in tyrosine hydroxylase (TH) heterozygous (TH+/-) and cAMP response element binding protein (CREB) binding protein (CBP) heterozygous (CBP+/-) mice. PCP (8 mg/kg) induced place preference in wild-type mice pretreated with PCP (10 mg/kg/day for 28 days) and increased the level of cAMP in the striatum, but not in the thalamus/hypothalamus. In TH+/- and CBP+/- mice, however, we could not find PCP-induced place preference. The increased level of cAMP in the striatum was observed in CBP+/-, but not TH+/- mice. When wild-type mice pretreated with morphine (10 mg/kg) twice a day for 5 days were challenged with naloxone (5 mg/kg), they showed increased jumping, rearing, and forepaw tremor counts as a sign of withdrawal and an increased level of cAMP in the thalamus/hypothalamus, but not in the striatum. In TH+/- and CBP+/- mice, however, jumping and forepaw tremor counts were decreased compared to in wild-type mice. An increase in the level of cAMP in the thalamus/hypothalamus in CBP+/-, but not in TH+/- mice was observed. These results suggest that catecholamines and CBP are involved in the development of PCP and morphine dependence, and that changes in catecholaminergic and/or cAMP systems induced by repeated PCP and morphine treatments play an important role in the addiction to PCP and morphine.

*Lectures presented at the 4th Congress of Toxicology in Developing Countries (4th CTOX-DC), Antalya, Turkey, 6-10 November 1999
**Corresponding author

Back to Contents for access to full text


Page last modified 13 September 2000.
Copyright © 2000 International Union of Pure and Applied Chemistry.
Questions or comments about IUPAC, please contact, the Secretariat.
Questions regarding the website, please contact web manager.