title: Nucleus accumbens NMDA receptor activation regulates amphetamine cross-sensitization and deltaFosB expression following sexual experience in male rats.
abstract: Sexual experience in male rats followed by a period of abstinence causes sensitization to d-Amphetamine (Amph) reward, evidenced by an increased conditioned place preference (CPP) for low doses of Amph. Moreover, sexual experience induces neural plasticity within the nucleus accumbens (NAc), including induction of deltaFosB, which plays a key role in Amph reward cross-sensitization. The NMDA receptor subunit NR1 is also upregulated by mating, but the functional relevance of NMDA receptors in sex experience-induced effects is unknown. Here, we examined the influence of intra-NAc MK 801 infusions on sex experience-induced NAc deltaFosB and cFos expression, as well as mating- and Amph-induced CPP in adult male rats. In experiment 1, males received MK 801 or saline into the NAc during each of 4 consecutive days of mating or handling and were tested for Amph CPP and experience-induced deltaFosB 10 days later. Intra-NAc MK 801 during sexual behavior prevented experience-induced increases in Amph CPP and NAc deltaFosB expression without affecting sexual behavior. In experiment 2, the effects of intra-NAc MK 801 on mating-induced CPP were examined by intra-NAc infusion of MK 801 or saline prior to mating on conditioning days. Intra-NAc MK 801 did not affect mating-induced CPP. Next, effects of intra-NAc MK 801 on mating-induced cFos immunoreactivity were examined. MK 801 prevented mating-induced cFos expression in NAc shell and core. Together, these results provide evidence that NAc NMDA receptor activation during sexual behavior plays a key role in mating-induced cFos and deltaFosB expression and subsequent experience-induced cross-sensitization to Amph reward.
authors.affiliation: Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA; Graduate Program in Neuroscience, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA.
authors.forename: Lauren N
authors.initials: LN
authors.lastname: Beloate
authors.affiliation: Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA; Graduate Program in Neuroscience, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA.
authors.forename: Peyton W
authors.initials: PW
authors.lastname: Weems
authors.affiliation: Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA.
authors.forename: Graham R
authors.initials: GR
authors.lastname: Casey
authors.affiliation: Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Webb
authors.affiliation: Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA; Department of Physiology & Biophysics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA. Electronic address: lcoolen@umc.edu.
authors.forename: Lique M
authors.initials: LM
authors.lastname: Coolen
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012201:Reward; D012726:Sexual Behavior, Animal / Q000502:physiology*
chemical_list: D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; C483820:Fosb protein, rat; C409466:NR1 NMDA receptor; D016760:Proto-Oncogene Proteins c-fos; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D000661:Amphetamine
keywords: Amphetamine; FosB; Glutamate; Sensitization; Striatum; cFos