Phencyclidine (PCP) is a major drug of abuse in the United States. Little is currently known of the effects of PCP on neuroendocrine function. Preliminary studies have shown that the acute administration of PCP increases the release of corticosterone and inhibits the release of prolactin and luteinizing hormone in the rat. The proposed series of experiments will characterize the effects of the acute and chronic administration of PCP on the release of these three anterior pituitary hormones in the rat. Drug-induced changes in behavior will also be measured in order to compare and contrast the effects of PCP on these two phenomenon. The involvement of opiate receptors in PCP-induced changes in neuroendocrine function will be evaluated by testing for antagonism by narcotic antagonists and cross-tolerance with morphine. The hypothesis that PCP and drugs with sigma opiate receptor activity share a common receptor will be tested by comparing the endocrine effects of PCP with those produced by enantiomers of N-allylnormetazocine as well as cross-tolerance to N-allylnormetazocine in chronically PCP-treated animals. PCP will also be injected directly into the cerebral ventricles in order to determine the role of central versus peripheral mechanisms in drug-induced neuroendocrine changes. These studies may provide a new in vivo model test system with which to characterize potential pathophysiological changes which occur with PCP use and lead to inferences regarding the underlying mechanisms of action of this drug on the central nervous system.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA004113-03
Application #
3209245
Study Section
(DABA)
Project Start
1986-06-01
Project End
1989-12-31
Budget Start
1988-06-01
Budget End
1989-12-31
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Pechnick, Robert N; Bresee, Catherine J; Poland, Russell E (2006) The role of antagonism of NMDA receptor-mediated neurotransmission and inhibition of the dopamine reuptake in the neuroendocrine effects of phencyclidine. Life Sci 78:2006-11
Pechnick, Robert N; Poland, Russell E (2004) Comparison of the effects of dextromethorphan, dextrorphan, and levorphanol on the hypothalamo-pituitary-adrenal axis. J Pharmacol Exp Ther 309:515-22
Kest, B; Mogil, J S; Sternberg, W F et al. (1995) 1,3-Di-o-tolylguanidine (DTG) differentially affects acute and tonic formalin pain: antagonism by rimcazole. Pharmacol Biochem Behav 52:175-8
Pechnick, R N; Hiramatsu, M (1994) The effects of MK-801 on body temperature and behavior in the rat: cross-sensitization and cross-tolerance with phencyclidine. Eur J Pharmacol 252:35-42
Kest, B; Mogil, J S; Sternberg, W F et al. (1994) Haloperidol increases pain behavior following peripheral tissue injury. Proc West Pharmacol Soc 37:89-90
Pechnick, R N; Poland, R E (1994) Neuroendocrine responses produced by enantiomeric pairs of drugs that interact with phencyclidine and sigma receptors. Eur J Pharmacol 263:115-20
Pechnick, R N (1993) Effects of opioids on the hypothalamo-pituitary-adrenal axis. Annu Rev Pharmacol Toxicol 33:353-82
Vargas, H M; Pechnick, R N (1991) Binding affinity and antimuscarinic activity of sigma and phencyclidine receptor ligands. Eur J Pharmacol 195:151-6
Bejanian, M; Pechnick, R N; Bova, M P et al. (1991) Effects of subcutaneous and intracerebroventricular administration of the sigma receptor ligand 1,3-Di-o-tolylguanidine on body temperature in the rat: interactions with BMY 14802 and rimcazole. J Pharmacol Exp Ther 258:88-93
Chung, L L; Pechnick, R N; Bova, M P et al. (1991) Acute and chronic administration of cocaine produces hyperthermia in the rat. Proc West Pharmacol Soc 34:27-8

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