It is the purpose of these experiments to examine the process of sensitization to cocaine following pretreatment with a number of pharmacological agents. It is our aim to evaluate the idea that at least part of the basis for variability in response to the rewarding effects of cocaine Is due to differences in the development of specific neurochemical systems, which in turn is due to environmental conditions. Rats will be exposed to four compounds (nicotine, caffeine, cocaine or amphetamine) for various periods of time. We will compare the ability for exposure to these compounds to alter the motor activating effects of cocaine and the propensity to self-administer this drug. Should the results show that preexposure to some agents can after the acquisition of cocaine self-administration, they will provide us with a realistic approach to prevention of abuse of this compound. We will also examine the neurochemical basis for changes in sensitivity produced by the preexposure regimen using microdialysis probes to measure the changes in extracellular dopamine within the nucleus accumbens and medial prefrontal cortex. Taken together, it is our hope that this line of investigation will demonstrate the importance of environmental factors as predisposing to drug abuse and will provide avenues leading to prevention of this compulsive self-destructive behavior.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA006825-03
Application #
2119100
Study Section
Drug Abuse Clinical and Behavioral Research Review Committee (DACB)
Project Start
1991-07-01
Project End
1995-06-30
Budget Start
1993-07-01
Budget End
1995-06-30
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Texas A&M University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
City
College Station
State
TX
Country
United States
Zip Code
77845
Schenk, S; Davidson, E S (1998) Stimulant preexposure sensitizes rats and humans to the rewarding effects of cocaine. NIDA Res Monogr 169:56-82
Schenk, S; Partridge, B (1997) Sensitization and tolerance in psychostimulant self-administration. Pharmacol Biochem Behav 57:543-50
Schenk, S; Partridge, B (1997) Effects of acute and repeated administration of N-methyl-D-aspartate (NMDA) into the ventral tegmental area: locomotor activating effects of NMDA and cocaine. Brain Res 769:225-32
Schenk, S; Worley, C M; McNamara, C et al. (1996) Acute and repeated exposure to caffeine: effects on reinstatement of extinguished cocaine-taking behavior in rats. Psychopharmacology (Berl) 126:17-23
Horger, B A; Valadez, A; Wellman, P J et al. (1994) Augmentation of the neurochemical effects of cocaine in the ventral striatum and medial prefrontal cortex following preexposure to amphetamine, but not nicotine: an in vivo microdialysis study. Life Sci 55:1245-51
Peltier, R L; Emmett-Oglesby, M W; Thomas, W H et al. (1994) Failure of ritanserin to block the discriminative or reinforcing stimulus effects of cocaine. Pharmacol Biochem Behav 48:473-8
Worley, C M; Valadez, A; Schenk, S (1994) Reinstatement of extinguished cocaine-taking behavior by cocaine and caffeine. Pharmacol Biochem Behav 48:217-21
Valadez, A; Schenk, S (1994) Persistence of the ability of amphetamine preexposure to facilitate acquisition of cocaine self-administration. Pharmacol Biochem Behav 47:203-5
McNamara, C G; Davidson, E S; Schenk, S (1993) A comparison of the motor-activating effects of acute and chronic exposure to amphetamine and methylphenidate. Pharmacol Biochem Behav 45:729-32
Schenk, S; Valadez, A; McNamara, C et al. (1993) Development and expression of sensitization to cocaine's reinforcing properties: role of NMDA receptors. Psychopharmacology (Berl) 111:332-8