Phencyclidine (PCP), also known as angel dust, is an important drug of abuse in the United States. In addition to producing profound changes in behavior, PCP disrupts neuroendocrine function and affects body temperature. While there are considerable data on the neurochemical basis of PCP-induced changes in behavior, there is little information on the neurochemical mechanisms underlying the effects of PCP on endocrine function and body temperature. The proposed studies will use selective agonists and antagonists to determine the role of sigma receptors in the effects of PCP on the release of ACTH and prolactin and in PCP-induced changes in body temperature in the rat. The hypothesis that dopaminergic and/or serotonergic mechanisms mediate some of the effects of PCP on neuroendocrine function and body temperature also will be tested by using selective antagonists, neurotransmitter synthesis inhibitors and neurotoxic lesions. Cocaine is known to affect dopaminergic and serotonergic neurotransmission, and possibly sigma receptors as well. The co-abuse of PCP and cocaine has become common on the street. Thus, from both a clinical and mechanistic standpoint, poly- and concurrent drug abuse is an important issue; however, there is little information on the physiological effects of this combination. The proposed studies also will characterize the effects of the co-administration of PCP and cocaine on neuroendocrine function and body temperature. Knowledge of the underlying fundamental mechanisms of action by which the effects of PCP are manifested is imperative in order to develop strategies with which the effects of PCP are manifested is imperative in order to develop strategies with which to prevent and possibly treat the sequelae of this major drug of abuse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA004113-06
Application #
3209247
Study Section
Special Emphasis Panel (SRCD (10))
Project Start
1986-06-01
Project End
1993-02-01
Budget Start
1992-01-01
Budget End
1993-02-01
Support Year
6
Fiscal Year
1992
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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