Animal research on addiction is stymied by a translational problem. Despite strides toward understanding circuit and molecular mechanisms of addiction, treatment options remain largely unchanged. This impasse is partly due to limitations in construct and predictive validity of animal models of addiction, which rarely incorporate social factors. To address this gap, Caprioli (the Principal Investigator) and others, developed an operant model to study incubation of methamphetamine (Meth) craving after choice-based voluntary abstinence where rats can choose between Meth or social interaction with a peer. They found that social-abstinence prevented the emergence of incubation of craving, a time-dependent increase in cue-induced drug seeking after abstinence from drug self-administration. Here we propose to investigate the neurobiological underpinnings of this phenomenon.
Based on the evidence that incubation of cocaine and Meth craving after forced abstinence is promoted by the accumulation of Ca2+-permeable AMPARs (CP-AMPARs) in nucleus accumbens (NAc) synapses we formulate our overarching hypothesis as follow: incubation of Meth craving is prevented by social self-administration via an attenuation of CP-AMPARs accumulation. We propose to use biochemical and electrophysiological approaches in two distinct experiments: 1) We will use western blot to determine the subunit composition of AMPARs in the NAc core (Aim 1)
and 2) patch clamp to determine the nature of excitatory transmission onto medium spiny neurons of the NAc (Aim 2) during incubation of Meth craving after forced and voluntary abstinence.
