Rats will learn to lever-press when they are rewarded by amphetamine injections into the nucleus accumbens, morphine injections into the ventral tegmental area, or electrical stimulation of the lateral hypothalamus. These three powerful rewards have a number of common consequences in addition to their ability to establish and maintain lever-press habits; each of the three stimulates locomotor activity, each increases feeding, and the amphetamine and morphine injections potentiate brain stimulation reward and cause learned place-preferences. The working hypothesis of the proposed studies is that these several effects all result from activation of a common system in the brain, and that this system has, as one of its elements, the mesolimbic dopamine system which has long been associated with each of these behaviors. The experimental strategy is to attempt to dissociate the various behaviors and the various rewards on the basis of behavioral, electrophysiological, pharmacological, and neurochemical comparisons. Do the same parameters and loci of brain stimulation produce each of these behaviors? Do the same drugs influence each of the stimulation effects? Do the same receptor-selective opioids produce locomotion, feeding, and place-preference: establish lever-pressing habits; and facilitate brain stimulation reward? Are the same amphetamine isomers and dopamine agonists and the same sites of injection associated with amphetamine's ability to cause each of these behavioral effects? Finally, do each of these rewards activate the mesolimbic dopamine system--as directly measured by in vivo voltammetry and micodialysis assay procedures- -and do each of the challenges of each of the rewards alter their effects on the dopamine system? The answers to these questions are important for a full understanding of the neurobiology of addiction, and they bear on the validity of specific treatment procedures currently in use with human addicts.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
2R37DA001720-13
Application #
3482626
Study Section
Pharmacology I Research Subcommittee (DABR)
Project Start
1977-04-01
Project End
1994-04-30
Budget Start
1989-08-01
Budget End
1990-04-30
Support Year
13
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Concordia University
Department
Type
DUNS #
City
Montreal
State
PQ
Country
Canada
Zip Code
H3G1M8
You, Z B; Chen, Y Q; Wise, R A (2001) Dopamine and glutamate release in the nucleus accumbens and ventral tegmental area of rat following lateral hypothalamic self-stimulation. Neuroscience 107:629-39
Kiyatkin, E A; Gratton, A (1994) Electrochemical monitoring of extracellular dopamine in nucleus accumbens of rats lever-pressing for food. Brain Res 652:225-34
Gratton, A; Wise, R A (1994) Drug- and behavior-associated changes in dopamine-related electrochemical signals during intravenous cocaine self-administration in rats. J Neurosci 14:4130-46
Devine, D P; Leone, P; Wise, R A (1993) Mesolimbic dopamine neurotransmission is increased by administration of mu-opioid receptor antagonists. Eur J Pharmacol 243:55-64
Carlezon Jr, W A; Wise, R A (1993) Morphine-induced potentiation of brain stimulation reward is enhanced by MK-801. Brain Res 620:339-42
Hoffman, D C; Wise, R A (1993) Lack of cross-sensitization between the locomotor-activating effects of bromocriptine and those of cocaine or heroin. Psychopharmacology (Berl) 110:402-8
Wolske, M; Rompre, P P; Wise, R A et al. (1993) Activation of single neurons in the rat nucleus accumbens during self-stimulation of the ventral tegmental area. J Neurosci 13:1-12
Devine, D P; Leone, P; Pocock, D et al. (1993) Differential involvement of ventral tegmental mu, delta and kappa opioid receptors in modulation of basal mesolimbic dopamine release: in vivo microdialysis studies. J Pharmacol Exp Ther 266:1236-46
Hoffman, D C; West, T E; Wise, R A (1991) Ventral pallidal microinjections of receptor-selective opioid agonists produce differential effects on circling and locomotor activity in rats. Brain Res 550:205-12
Gerber, G J; Wise, R A (1989) Pharmacological regulation of intravenous cocaine and heroin self-administration in rats: a variable dose paradigm. Pharmacol Biochem Behav 32:527-31

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