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. These changes not only participate in the acute and chronic drug effects, but also can be used to provide information on the underlying mechanisms of drug action. Although there is a large volume of information on the neurochemical basis of PCP-induced changes in behavior, little is known about the neurochemical mechanisms mediating the effects of PCP on neuroendocrine function and body temperature. The overall goal of the proposed studies is to define the role of N-methyl-D-aspartate (NMDA) and monoaminergic systems in the effects of PCP on the hypothalamic-pituitary-adrenal (HPA) axis and body temperature. The proposed studies will characterize the effects of both competitive NMDA antagonists and glycine antagonists in order to determine whether stimulation of the HPA axis and changes in body temperature are general properties of compounds that inhibit NMDA receptor-mediated neurotransmission. Interactions between the various binding sites on the NMDA receptor also will be assessed by determining whether competitive antagonists and glycine antagonists can reduce the effects of PCP and MK- 801 on the HPA axis and body temperature. The role of monoaminergic systems in producing some of the effects of PCP and MK-801 on neuroendocrine function and body temperature will be evaluated by using selective monoaminergic receptor antagonists. Knowledge of the fundamental mechanisms of action by 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 important drug of abuse. The proposed studies also will generate new information on the effects of inhibiting NMDA receptor-mediated neurotransmission. As the NMDA receptor is thought to play a major role in development, learning and memory, seizure and mental disorders as well as neurotoxicity, studying the effects of PCP and its interactions with NMDA receptors may lead to new and important information outside of the area of drug abuse that could increase our understanding of the etiology and the treatment of neurological and mental disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA004113-10
Application #
2012866
Study Section
Special Emphasis Panel (SRCD (14))
Project Start
1986-06-01
Project End
1998-12-31
Budget Start
1997-01-01
Budget End
1998-12-31
Support Year
10
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Louisiana State University Hsc New Orleans
Department
Pharmacology
Type
Schools of Medicine
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
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
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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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