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

Toshitaka Nabeshima, Takayoshi Mamiya, Yukihiro Noda

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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.

Original languageEnglish
Pages (from-to)1035-1044
Number of pages10
JournalPure and Applied Chemistry
Volume72
Issue number6
DOIs
Publication statusPublished - 01-01-2000
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Chemical Engineering(all)

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