Acute methamphetamine produces long-term deficits in hippocampal- | 48864

Journal of Neuroscience and Neuropharmacology

Acute methamphetamine produces long-term deficits in hippocampal- dependent spatial learning and memory retention, decreases PKMzeta and dopamine 1 receptors (D1), and increases microglial and prostaglandin J2 expression

4th Global Experts Meeting on Neuropharmacology

September 14-16, 2016 San Antonio, USA

Peter A Serrano

Hunter College, USA
The Graduate Center of CUNY, USA

Posters & Accepted Abstracts: Neurochem Neuropharm

Abstract :

We evaluated the effects of methamphetamine on spatial learning and memory using the hippocampal dependent task, the radial 8-arm maze (RAM). Hippocampus was analyzed for synaptic markers important for memory and synaptic plasticity including the D1 receptor, the atypical protein kinase M zeta (PKM√?¬∂), and the AMPA receptor subunit GluA2. PKM√?¬∂ is important for trafficking the GluA2 subunit to the membrane. Maintaining GluA2 on the synaptic membrane improves memory retention. We hypothesize that neuroinflammation plays a role in exacerbating the negative effects of MA-induced learning and memory deficits. One inflammatory marker in particular, cyclooxygenase-2 (COX 2) catalyzes the conversion of arachidonic acid into prostaglandins. Several prostaglandins are catalyzed by COX2, but one in particular is very toxic, the prostaglandin J2 (PGJ2). Thus, we are interested in determining how MA toxicity may activate this inflammatory pathway, perpetuating the toxicity leading to sustained cognitive deficits. Our results show MA produces deficits in learning the RAM after 6 weeks of abstinence. This was correlated with a decrease in PKM√?¬∂ and D1 expression and increase in COX-2, PGJ2 and ubiquinated protiens. Additionally, bolus doses of MA (once per week for 3 weeks) after completing RAM training, results in memory retrieval deficits. Analyses of the hippocampus shows increased microglia expression and impaired trafficking of GluA2 in hippocampal area CA3. These data show that short-term acute binge doses of MA followed by long-term abstinence produce chronic inflammation that disrupts trafficking of synaptic markers that may exacerbate and/or sustain the long-term spatial memory deficits induced by MA.

Biography :