The purpose of this research is to provide a foundation for understanding the inheritance of sensitivity to the effects of cocaine and other psychomotor stimulants. The basic hypothesis is that behavioral stimulants like cocaine, amphetamine and caffeine produce their effects by initially interacting with different biochemical systems. This is most clearly demonstrated by describing the separable effects of these drugs in inbred mice and their recombinant inbred lines. The proposed studies will examine the effects of cocaine, norcocaine, methylphenidate and d-amphetamine on mouse body temperature, spontaneous locomotor activity, operant behavior and drug discrimination tasks. Both the progenitor strains (e.g. C57BL/6, DBA/2J) and recombinant inbred lines (e.g. BXD-11, BXD21, etc) will be used to study the separable or associated inheritance of sensitivity to these drug effects. Chronic administration of each of the stimulants will be studied to determine the relationship between acute effects and the magnitude of tolerance or sensitization observed.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA004028-04
Application #
3209017
Study Section
Drug Abuse Clinical and Behavioral Research Review Committee (DACB)
Project Start
1988-02-01
Project End
1990-02-28
Budget Start
1988-04-01
Budget End
1989-02-28
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Kentucky
Department
Type
Schools of Medicine
DUNS #
832127323
City
Lexington
State
KY
Country
United States
Zip Code
40506
Seale, T W; Carney, J M (1991) Genetic determinants of susceptibility to the rewarding and other behavioral actions of cocaine. J Addict Dis 10:141-62
Carney, J M; Landrum, R W; Cheng, M S et al. (1991) Establishment of chronic intravenous drug self-administration in the C57BL/6J mouse. Neuroreport 2:477-80
Carney, J M; Tolliver, B; Carney, J P et al. (1991) Selective effects of behaviorally active doses of methamphetamine on mRNA expression in the gerbil brain. Neuropharmacology 30:1011-9
Kindy, M S; Carney, J P; Dempsey, R J et al. (1991) Ischemic induction of protooncogene expression in gerbil brain. J Mol Neurosci 2:217-28
Logan, L; Seale, T W; Cao, W et al. (1988) Effects of chronic amphetamine in BALB/cBy mice, a strain that is not stimulated by acute administration of amphetamine. Pharmacol Biochem Behav 31:675-82
Seale, T W; Abla, K A; Roderick, T H et al. (1987) Different genes specify hyporesponsiveness to seizures induced by caffeine and the benzodiazepine inverse agonist, DMCM. Pharmacol Biochem Behav 27:451-6
Seale, T W; Abla, K A; Cao, W et al. (1986) Inherent hyporesponsiveness to methylxanthine-induced behavioral changes associated with supersensitivity to 5'-N-ethylcarboxamidoadenosine (NECA). Pharmacol Biochem Behav 25:1271-7
Carney, J M; Cao, W; Logan, L et al. (1986) Differential antagonism of the behavioral depressant and hypothermic effects of 5'-(N-ethylcarboxamide) adenosine by theobromine. Pharmacol Biochem Behav 25:769-73