Abstract

This is a proposal to investigate neurotensin and cholecystokinin in the function of the mesolimbic dopamine system using behavioral and neurochemical tests. Studies will focus on the ventral tegmental area (VTA) and the nucleus accumbens (NAC). This project grows out of reports that rats will self-inject morphine and neurotensin in the VTA and will self-inject amphetamine, dopamine and cholecystokinin in the NAC. It appears that animals work for chemical control over the mesolimbic system. In addition, it has been reported that the stimulus properties of i.p. amphetamine generalize to NAC amphetamine, and that dopamine and cholecystokinin can act synergistically to induce locomotion. We propose to study neurotensin and cholecystokinin, mprphine and amphetamine, and dopamine by a dose-response analysis of their reinforcing and stimulus generalization properties. Positive results with these agonists will be followed up with (a) receptor antagonists to determine relevance to synaptic neuropharmacology, (b) 6-hydroxy-dopamine to determine dependence on mesolimbic dopamine release, (c) regional assays to measure dopamine turnover, and (d) local dialysis to measure catecholamine and cholecystokinin release. This proposal will clarify the function of neurotensin and cholecystokinin in modulating the mesolimbic system and their relation to morphine and amphetamine.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA003597-03
Application #
3208110
Study Section
(DABA)
Project Start
1985-07-01
Project End
1988-12-31
Budget Start
1987-07-01
Budget End
1988-12-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
Princeton University
Department
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544

  Publications

Mark, G P; Weinberg, J B; Rada, P V et al. (1995) Extracellular acetylcholine is increased in the nucleus accumbens following the presentation of an aversively conditioned taste stimulus. Brain Res 688:184-8
Mark, G P; Smith, S E; Rada, P V et al. (1994) An appetitively conditioned taste elicits a preferential increase in mesolimbic dopamine release. Pharmacol Biochem Behav 48:651-60
Rada, P V; Mark, G P; Hoebel, B G (1993) In vivo modulation of acetylcholine in the nucleus accumbens of freely moving rats: I. Inhibition by serotonin. Brain Res 619:98-104
Rada, P V; Mark, G P; Hoebel, B G (1993) In vivo modulation of acetylcholine in the nucleus accumbens of freely moving rats: II. Inhibition by gamma-aminobutyric acid. Brain Res 619:105-10
Hoebel, B G; Hernandez, L; Mark, G P et al. (1992) Microdialysis in the study of psychostimulants and the neural substrate for reinforcement: focus on dopamine and serotonin. NIDA Res Monogr 124:1-34
Hernandez, L; Parada, M; Baptista, T et al. (1991) Hypothalamic serotonin in treatments for feeding disorders and depression as studied by brain microdialysis. J Clin Psychiatry 52 Suppl:32-40
Rada, P; Mark, G P; Pothos, E et al. (1991) Systemic morphine simultaneously decreases extracellular acetylcholine and increases dopamine in the nucleus accumbens of freely moving rats. Neuropharmacology 30:1133-6
Hernandez, L; Guzman, N A; Hoebel, B G (1991) Bidirectional microdialysis in vivo shows differential dopaminergic potency of cocaine, procaine and lidocaine in the nucleus accumbens using capillary electrophoresis for calibration of drug outward diffusion. Psychopharmacology (Berl) 105:264-8
Rada, P; Pothos, E; Mark, G P et al. (1991) Microdialysis evidence that acetylcholine in the nucleus accumbens is involved in morphine withdrawal and its treatment with clonidine. Brain Res 561:354-6
Hernandez, L; Hoebel, B G (1990) Feeding can enhance dopamine turnover in the prefrontal cortex. Brain Res Bull 25:975-9

Showing the most recent 10 out of 21 publications