Mediodorsal nucleus of the thalamus is critical for the expression of memory of methamphetamine-produced conditioned place preference in rats

Methamphetamine (MA) is a powerful and highly addictive psychostimulant. However, the neural substrate mediating MA-induced conditioned effects, an essential part of addiction, remain unclear. The present study investigated the involvement of the anterior cingulate cortex (ACC), the lateral nucleus of amygdala (LNA), and the mediodorsal nucleus of the thalamus (MD) in MA-conditioned place preference (CPP). Rats underwent bilateral radio-frequency lesions of the ACC, LNA, or MD followed by MA CPP training. Lesions of the MD, but not the ACC or LNA, disrupted MA CPP learning. To clarify the role of the MD on the different stages of the MA CPP memory process, bilateral microinfusions of lidocaine into the MD were performed 5 min prior to each conditioning trial, immediately after the conditioning trial, or 5 min before the testing phase. Pretesting, but not pre- or post-conditioning, infusions of lidocaine into the MD impaired MA CPP. Furthermore, a clear preference for the previously conditioned MA paired cues was expressed when the rats were tested again 24 h after infusions of lidocaine. These results are interpreted as indicating that the MD is specifically involved in the memory retrieval process of MA associated memory which suggests the MD could have an important role in relapse in individuals suffering from MA addiction.

Research highlights▶Lesions of mediodorsal nucleus of thalamus (MD) disrupt methamphetamine (MA) CPP. ▶Anterior cingulate cortex or lateral nucleus of amygdala is not involved in MA CPP. ▶MD is critical for retrieval, but not acquisition of MA-associated memory.