BDNF Over-Expression in the Ventral Tegmental Area Prolongs Social Defeat Stress-Induced Cross-Sensitization to Amphetamine and Increases ?FosB Expression in Mesocorticolimbic Regions of Rats.

BDNF Over-Expression in the Ventral Tegmental Area Prolongs Social Defeat Stress-induced Cross-Sensitization to Amphetamine and Increases ?FosB Expression in Mesocorticolimbic Regions of Rats.

Neuropsychopharmacology. 2013 May 21;
Wang J, Fanous S, Terwilliger EF, Bass CE, Hammer RP, Nikulina EM

Social defeat stress induces persistent cross-sensitization to psychostimulants, but the molecular mechanisms underlying the development of cross-sensitization remain unclear. One candidate is brain-derived neurotrophic factor (BDNF). The present research examined whether ventral tegmental area (VTA) BDNF over-expression would prolong the time-course of cross-sensitization after a single social defeat stress, which normally produces transient cross-sensitization lasting less than one week. ?FosB, a classic molecular marker of addiction, was also measured in mesocorticolimbic terminal regions. Separate groups of intact male Sprague-Dawley rats underwent a single episode of social defeat stress or control handling, followed by amphetamine challenge 3 or 14 days later. AMPH cross-sensitization was apparent 3 but not 14 days after stress. Intra-VTA infusion of adeno-associated viral (AAV-BDNF) vector resulted in a two-fold increase of BDNF level in comparison with the group receiving the control virus (AAV-GFP), which lasted at least 45 days. Additionally, over-expression of BDNF in the VTA alone increased ?FosB in the nucleus accumbens (NAc) and prefrontal cortex. Fourteen days after viral infusions, a separate group of rats underwent a single social defeat stress or control handling and were challenged with amphetamine (AMPH) 14 and 24 days after stress. AAV-BDNF rats exposed to stress showed prolonged cross-sensitization and facilitated sensitization to the second drug challenge. Immunohistochemistry showed that the combination of virally enhanced VTA BDNF, stress, and AMPH resulted in increased ?FosB in the NAc shell compared to other groups. Thus, elevation of VTA BDNF prolongs cross-sensitization, facilitates sensitization, and increases ?FosB in mesocorticolimbic terminal regions. As such, elevated VTA BDNF may be a risk factor for drug sensitivity.Neuropsychopharmacology accepted article preview online, 21 May 2013; doi:10.1038/npp.2013.130. HubMed – addiction


Addiction Science: Uncovering Neurobiological Complexity.

Neuropharmacology. 2013 May 17;
Volkow ND, Baler RD

Until very recently addiction-research was limited by existing tools and strategies that were inadequate for studying the inherent complexity at each of the different phenomenological levels. However, powerful new tools (e.g., optogenetics and designer drug receptors) and high throughput protocols are starting to give researchers the potential to systematically interrogate “all” genes, epigenetic marks, and neuronal circuits. These advances, combined with imaging technologies (both for preclinical and clinical studies) and a paradigm shift towards open access have spurred an unlimited growth of datasets transforming the way we investigate the neurobiology of substance use disorders (SUD) and the factors that modulate risk and resilience. HubMed – addiction


Neurologic Manifestations of Chronic Methamphetamine Abuse.

Psychiatr Clin North Am. 2013 Jun; 36(2): 261-275
Rusyniak DE

The drug with perhaps the greatest impact on the practice of Psychiatry is Methamphetamine. By increasing the extracellular concentrations of dopamine while slowly damaging the dopaminergic neurotransmission, Meth is a powerfully addictive drug whose chronic use preferentially causes psychiatric complications. Chronic Meth users have deficits in memory and executive functioning as well as higher rates of anxiety, depression, and most notably psychosis. It is because of addiction and chronic psychosis from Meth abuse that the Meth user is most likely to come to the attention of the practicing Psychiatrist/Psychologist. Understanding the chronic neurologic manifestations of Meth abuse will better arm practitioners with the diagnostic and therapeutic tools needed to make the Meth epidemic one of historical interest only. HubMed – addiction