Role of Anterior Intralaminar Nuclei of Thalamus Projections to Dorsomedial Striatum in Incubation of Methamphetamine Craving

Relapse to methamphetamine (Meth) seeking progressively increases after withdrawal from drug self-administration (incubation of Meth craving). We previously demonstrated a role of dorsomedial striatum (DMS) dopamine D1 receptors (D1Rs) in this incubation. Here, we studied the role of afferent glutamatergic projections into the DMS and local D1R-glutamate interaction in this incubation in male rats. We first measured projection-specific activation on day 30 relapse test by using cholera toxin b (retrograde tracer) + Fos (activity marker) double-labeling in projection areas. Next, we determined the effect of pharmacological reversible inactivation of lateral or medial anterior intralaminar nuclei of thalamus (AIT-L or AIT-M) on incubated Meth seeking on withdrawal day 30. We then used an anatomical asymmetrical disconnection procedure to determine whether an interaction between AIT-L -> DMS glutamatergic projections and postsynaptic DMS D1Rs contributes to incubated Meth seeking. We also determined the effect of unilateral inactivation of AIT-L and D1R blockade of DMS on incubated Meth seeking, and the effect of contralateral disconnection of AIT-L -> DMS projections on nonincubated Meth seeking on withdrawal day 1. Incubated Meth seeking was associated with selective activation of AIT -> DMS projections; other glutamatergic projections to DMS were not activated. AIT-L (but not AIT-M) inactivation or anatomical disconnection of AIT-L -> DMS projections decreased incubated Meth seeking. Unilateral inactivation of AIT-L or D1R blockade of the DMS had no effect on incubated Meth craving, and contralateral disconnection of AIT-L -> DMS projections had no effect on nonincubated Meth seeking. Our results identify a novel role of AIT-L and AIT-L -> DMS glutamatergic projections in incubation of drug craving and drug seeking