title: Endogenous opioid-induced neuroplasticity of dopaminergic neurons in the ventral tegmental area influences natural and opiate reward.
abstract: Natural reward and drugs of abuse converge on the mesolimbic pathway and activate common mechanism of neural plasticity in the nucleus accumbens. Chronic exposure to opiates induces plasticity in dopaminergic neurons of the ventral tegmental area (VTA), which regulates morphine reward tolerance. Here, we test the hypotheses that mating-induced release of endogenous opioids in the VTA causes morphological changes of VTA dopamine cells in male rats, which in-turn regulate the long-term expression of experience-induced reinforcement of sexual behavior. First, sexual experience decreased VTA dopamine soma size 1 and 7 days, but not 30 days after the last mating session. This effect was blocked with naloxone before each mating session; thus, VTA dopamine cell plasticity was dependent on action of endogenous opioids. In turn, VTA plasticity was associated with altered opiate reward, as sexually experienced males did not form conditioned place preference for 0.5 mg/kg morphine. Next, it was determined whether endogenous opioid action mediates sexual reward and memory in male rats treated with naloxone during mating experience, either systemically or intra-VTA. Naloxone did not prevent the initial experience-induced facilitation of sexual behavior over repeated mating sessions, or conditioned place preference for mating. However, naloxone treatment attenuated the longer-term expression of experience-induced facilitation of sexual behavior and neural activation in mesolimbic areas induced by mating-associated conditioned cues. Together, these data demonstrate that endogenous opioids during mating induce neural plasticity in VTA dopamine neurons that appear critical for morphine reward and long-term memory for natural reward behavior.
authors: Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada N6A 3K7, Department of Psychology, University of Michigan, Ann Arbor, Michigan 48109.
authors: Kyle K
authors: KK
authors: Pitchers
authors: Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada N6A 3K7.
authors: Caroline M
authors: CM
authors: Coppens
authors: Departments of Neurobiology and Anatomical Sciences, and.
authors: Lauren N
authors: LN
authors: Beloate
authors: Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada N6A 3K7.
authors: Jonathan
authors: J
authors: Fuller
authors: Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada N6A 3K7.
authors: Sandy
authors: S
authors: Van
authors: Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada N6A 3K7.
authors: Karla S
authors: KS
authors: Frohmader
authors: Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada N6A 3K7.
authors: Steven R
authors: SR
authors: Laviolette
authors: Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada N6A 3K7, Departments of Neurobiology and Anatomical Sciences, and.
authors: Michael N
authors: MN
authors: Lehman
authors: Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada N6A 3K7, Department of Psychology, University of Michigan, Ann Arbor, Michigan 48109, Departments of Neurobiology and Anatomical Sciences, and Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi 39216 lcoolen@umc.edu.
authors: Lique M
authors: LM
authors: Coolen
mesh_terms: D000818:Animals; D001245:Association Learning / Q000187:drug effects / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D003307:Copulation / Q000502:physiology*; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology*
chemical_list: D009292:Narcotic Antagonists; D009270:Naloxone; D009020:Morphine
keywords: dopamine; memory; mesolimbic; morphine; reward; ventral tegmental area