This application is a competing continuation of a Research Scientist Development Award (RSDA) to Charles P. France, currently a Professor of Pharmacology and Experimental Therapeutics and Neuroscience at Louisiana State University (LSU) Medial Center in New Orleans. The overall objectives of research in the candidate's laboratory are to develop reliable drug discrimination procedures for studying drug dependence and withdrawal in non-human species, to use those procedures to examine the dependence potential and the therapeutic potential of a wide range of drugs, and to integrate these behavioral findings with other clinically-relevant measures of drug action. These studies also focus on the receptor mechanisms that mediate the abuse-related effects of drugs by structuring experiments around testable hypotheses that are founded in and guided by receptor theory. This combined approach, whereby behavioral procedures are used in concert with receptor theory, provides a bridge from molecular science to the clinic. During the initial period of support the breadth of research in the candidate's laboratory increased markedly to include studies on: benzodiazepine dependence and withdrawal; self- administration procedures in rats and monkeys; the effects of contingent and non-contingent cocaine administration on cognitive function (learning and memory) and on the hypothalamic-pituitary-adrenal (HPA) axis; as well as endocrine and immune responses to acute and chronic drug treatment.
The specific aims i n this competing renewal are to evaluate opioids and GABAA modulators (e.g. benzodiazepines) for physical dependence potential, abuse liability and toxicity using drug discrimination, ventilation, antinociception, self-administration, and repeated acquisition procedures as well as schedule-controlled behavior and measures of immune and endocrine function. To augment ongoing and future behavioral studies on efficacy, the candidate plans to initiate a binding assay that is sensitive to variations in efficacy (GTPgammaS binding). Renewal of the RSDA will relieve the candidate of otherwise substantial teaching and administrative responsibilities and, thereby, allow him to fully participate in the research projects that have been initiated during the current period of support, collaborate extensively with other NIH-supported investigators at LSU Medical Center, and spend time training young scientists in his laboratory.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02DA000211-07
Application #
6150436
Study Section
Special Emphasis Panel (ZDA1-MXS-M (01))
Program Officer
Schnur, Paul
Project Start
1994-02-10
Project End
2000-05-31
Budget Start
2000-02-15
Budget End
2000-05-31
Support Year
7
Fiscal Year
2000
Total Cost
$37,261
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
Boctor, Sherin Y; Martinez Jr, Joe L; Koek, Wouter et al. (2007) The cannabinoid CB1 receptor antagonist AM251 does not modify methamphetamine reinstatement of responding. Eur J Pharmacol 571:39-43
Williams, Jason M; Owens, W Anthony; Turner, Gregory H et al. (2007) Hypoinsulinemia regulates amphetamine-induced reverse transport of dopamine. PLoS Biol 5:e274
Owens, W Anthony; Sevak, Rajkumar J; Galici, Ruggero et al. (2005) Deficits in dopamine clearance and locomotion in hypoinsulinemic rats unmask novel modulation of dopamine transporters by amphetamine. J Neurochem 94:1402-10
Galici, Ruggero; Galli, Aurelio; Jones, David J et al. (2003) Selective decreases in amphetamine self-administration and regulation of dopamine transporter function in diabetic rats. Neuroendocrinology 77:132-40
McMahon, L R; France, C P (2002) Acute and chronic effects of the neuroactive steroid pregnanolone on schedule-controlled responding in rhesus monkeys. Behav Pharmacol 13:545-55
Brandt, M R; Galici, R; France, C P (2000) The discriminative stimulus effects of morphine in pigeons responding under a progressive ratio schedule of food presentation. Behav Pharmacol 11:15-28
Winsauer, P J; Silvester, K R; Moerschbaecher, J M et al. (2000) Cocaine self-administration in monkeys: effects on the acquisition and performance of response sequences. Drug Alcohol Depend 59:51-61
Gauthier, C A; Bagley, J R; Brockunier, L L et al. (1999) Daily mirfentanil induces (cross-) tolerance to the rate-decreasing effects of morphine and not mirfentanil. Behav Pharmacol 10:543-7
France, C P; Gerak, L R (1994) Behavioral effects of 6-methylene naltrexone (nalmefene) in rhesus monkeys. J Pharmacol Exp Ther 270:992-9
Carr, D J; Baker, M L; Holmes, C et al. (1994) OHM3295: a fentanyl-related 4-heteroanilido piperidine with analgesic effects but not suppressive effects on splenic NK activity in mice. Int J Immunopharmacol 16:835-44