Studies of food, water and brain-stimulation rewards have provided evidence that central dopaminergic (DA) substrates represent an important link in the neurobiology of positive reinforcement. Since abused drugs are presumed to act via a central activation of the brain's natural reward mechanism(s) it has been suggested that these DA pathways also mediate the reinforcing properties of self-administered drugs. Controversy exists, however, over whether or not such DA systems underlie the reward produced by all positive reinforcers or whether various independent systems exist in parallel within the CNS. The proposed research was devised to test the hypothesis that central DA neurons mediate the reinforcing properties of two major classes of abused drugs - the psychomotor stimulants (amphetamine, cocaine), and the opiate agonists (morphine and heroin). the effects of peripheral and central DA receptor antagonists on drug reward shall be examined in two novel behavioral paradigms: a Partial Reinforcement Extinction Test and an Incentive Motivation test. Both tests have the important advantage of assessing reward changes in animals that are no longer drugged at the time of testing. The proposed research should a) provide information relevant to our understanding of human stimulant and opiate drug abuse; and b) help elucidate the role of central DA neurons in the neural basis of drug reward.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA005041-02
Application #
3211015
Study Section
(SRCD)
Project Start
1988-03-01
Project End
1991-02-28
Budget Start
1989-03-01
Budget End
1990-02-28
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Chicago
Department
Type
Schools of Social Welfare/Work
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
Ettenberg, Aaron; Fomenko, Vira; Kaganovsky, Konstantin et al. (2015) On the positive and negative affective responses to cocaine and their relation to drug self-administration in rats. Psychopharmacology (Berl) 232:2363-75
Wenzel, Jennifer M; Cotten, Samuel W; Dominguez, Hiram M et al. (2014) Noradrenergic ?-receptor antagonism within the central nucleus of the amygdala or bed nucleus of the stria terminalis attenuates the negative/anxiogenic effects of cocaine. J Neurosci 34:3467-74
Wenzel, Jennifer M; Su, Zu-In; Shelton, Kerisa et al. (2013) The dopamine antagonist cis-flupenthixol blocks the expression of the conditioned positive but not the negative effects of cocaine in rats. Pharmacol Biochem Behav 114-115:90-6
Su, Zu-In; Santoostaroam, Ashley; Wenzel, Jennifer et al. (2013) On the persistence of cocaine-induced place preferences and aversions in rats. Psychopharmacology (Berl) 229:115-23
Kerstetter, Kerry A; Su, Zu-In; Ettenberg, Aaron et al. (2013) Sex and estrous cycle differences in cocaine-induced approach-avoidance conflict. Addict Biol 18:222-9
Su, Zu-In; Kichaev, Gleb; Wenzel, Jennifer et al. (2012) Weakening of negative relative to positive associations with cocaine-paired cues contributes to cue-induced responding after drug removal. Pharmacol Biochem Behav 100:458-63
Ettenberg, Aaron; Ofer, Oren A; Mueller, Carl L et al. (2011) Inactivation of the dorsal raphe nucleus reduces the anxiogenic response of rats running an alley for intravenous cocaine. Pharmacol Biochem Behav 97:632-9
Wenzel, Jennifer M; Waldroup, Stephanie A; Haber, Zachary M et al. (2011) Effects of lidocaine-induced inactivation of the bed nucleus of the stria terminalis, the central or the basolateral nucleus of the amygdala on the opponent-process actions of self-administered cocaine in rats. Psychopharmacology (Berl) 217:221-30
Su, Zu-In; Wenzel, Jennifer; Baird, Rebeccah et al. (2011) Comparison of self-administration behavior and responsiveness to drug-paired cues in rats running an alley for intravenous heroin and cocaine. Psychopharmacology (Berl) 214:769-78
Moscarello, J M; Ben-Shahar, O; Ettenberg, A (2010) External incentives and internal states guide goal-directed behavior via the differential recruitment of the nucleus accumbens and the medial prefrontal cortex. Neuroscience 170:468-77

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