title: The Roles of Dopamine and α1-Adrenergic Receptors in Cocaine Preferences in Female and Male Rats.
abstract: Cocaine dependence is characterized by compulsive drug taking and reduced involvement in social, occupational, or recreational activities. Unraveling the diverse mechanisms contributing to the loss-of-interest in these 'non-drug' pursuits is essential for understanding the neurobiology of addiction and could provide additional targets for treating addiction. The study objectives were to examine changes in cocaine-induced dopamine (DA) overflow in the nucleus accumbens (NAc) over the course of self-administration and determine the roles of α1- and β-adrenergic receptors (AR) in the loss-of-interest in food rewards following the development of an addicted phenotype in male and female rats. Subjects were given access to cocaine and palatable food pellets in a choice self-administration paradigm to identify 'addicted' cocaine-preferring (CP) individuals and resistant pellet-preferring (PP) individuals based on their patterns of self-administration over 7 weeks. Cocaine-induced DA overflow in the NAc was examined with microdialysis early and late during self-administration (weeks 2 and 7). Subjects were treated in counter-balanced order with propranolol (β-AR antagonist), terazosin (α1-AR antagonist), or vehicle for an additional 3 weeks of self-administration. CP rats displayed increased motivation for cocaine and attenuated motivation for pellets following the development of cocaine preferences. In females, the estrous cycle affected pellet, but not cocaine, self-administration. CP rats displayed attenuated cocaine-induced DA overflow in the NAc. Propranolol enhanced cocaine reinforcement and reduced pellet intake, whereas terazosin enhanced motivation for pellets and reversed preferences in a subset of CP rats. The implications of these results for the treatment of addiction are discussed.
authors.affiliation: Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Adam N
authors.initials: AN
authors.lastname: Perry
authors.affiliation: Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Christel
authors.initials: C
authors.lastname: Westenbroek
authors.affiliation: Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Lakshmikripa
authors.initials: L
authors.lastname: Jagannathan
authors.affiliation: Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.|Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.|Department of Psychology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Jill B
authors.initials: JB
authors.lastname: Becker
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D016739:Behavior, Addictive / Q000503:physiopathology / Q000523:psychology; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D008297:Male; D017551:Microdialysis; D009042:Motivation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism*; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration; D012727:Sex Characteristics; D018709:Statistics, Nonparametric
chemical_list: D018663:Adrenergic Agents; D018765:Dopamine Uptake Inhibitors; D018340:Receptors, Adrenergic, alpha-1; D011954:Receptors, Dopamine; D003042:Cocaine