Natural and Drug Rewards Act on Common Neural Plasticity Mechanisms With ?FosB as a Key Mediator.

Natural and Drug Rewards Act on Common Neural Plasticity Mechanisms with ?FosB as a Key Mediator.

J Neurosci. 2013 Feb 20; 33(8): 3434-3442
Pitchers KK, Vialou V, Nestler EJ, Laviolette SR, Lehman MN, Coolen LM

Drugs of abuse induce neuroplasticity in the natural reward pathway, specifically the nucleus accumbens (NAc), thereby causing development and expression of addictive behavior. Recent evidence suggests that natural rewards may cause similar changes in the NAc, suggesting that drugs may activate mechanisms of plasticity shared with natural rewards, and allowing for unique interplay between natural and drug rewards. In this study, we demonstrate that sexual experience in male rats when followed by short or prolonged periods of loss of sex reward causes enhanced amphetamine reward, indicated by sensitized conditioned place preference for low-dose (0.5 mg/kg) amphetamine. Moreover, the onset, but not the longer-term expression, of enhanced amphetamine reward was correlated with a transient increase in dendritic spines in the NAc. Next, a critical role for the transcription factor ?FosB in sex experience-induced enhanced amphetamine reward and associated increases in dendritic spines on NAc neurons was established using viral vector gene transfer of the dominant-negative binding partner ?JunD. Moreover, it was demonstrated that sexual experience-induced enhanced drug reward, ?FosB, and spinogenesis are dependent on mating-induced dopamine D1 receptor activation in the NAc. Pharmacological blockade of D1 receptor, but not D2 receptor, in the NAc during sexual behavior attenuated ?FosB induction and prevented increased spinogenesis and sensitized amphetamine reward. Together, these findings demonstrate that drugs of abuse and natural reward behaviors act on common molecular and cellular mechanisms of plasticity that control vulnerability to drug addiction, and that this increased vulnerability is mediated by ?FosB and its downstream transcriptional targets. HubMed – addiction
Gambling rats and gambling addiction: reconciling the role of dopamine in irrationality.

J Neurosci. 2013 Feb 20; 33(8): 3256-8
Sescousse G, den Ouden HE

HubMed – addiction
Ethanol Effects on N-Methyl-D-Aspartate Receptors in the Bed Nucleus of the Stria Terminalis.

Cold Spring Harb Perspect Med. 2013 Feb 20;
Wills TA, Winder DG

The extended amygdala is a series of interconnected, embryologically similar series of nuclei in the brain that are thought to play key roles in aspects of alcohol dependence, specifically in stress-induced increases in alcohol-seeking behaviors. Plasticity of excitatory transmission in these and other brain regions is currently an intense area of scrutiny as a mechanism underlying aspects of addiction. N-methyl-d-aspartate (NMDA) receptors (NMDARs) play a critical role in plasticity at excitatory synapses and have been identified as major molecular targets of ethanol. Thus, this article will explore alcohol and NMDAR interactions first at a general level and then focusing within the extended amygdala, in particular on the bed nucleus of the stria terminalis (BNST). HubMed – addiction