Methamphetamine seeking after prolonged abstinence is associated with activated projections from anterior intralaminar nucleus of thalamus to dorsolateral striatum in female rats

Methamphetamine (Meth) seeking progressively increases after cessation from drug self-administration (incubation of Meth craving). We have previously shown that both dorsomedial and dorsolateral striatum (DMS and DLS) play critical roles in this incubation in male rats. Moreover, our recent anatomical tracing study examined afferent projections into DMS and demonstrated a novel role of projections from anterior intralaminar nucleus of thalamus (AIT) to DMS in incubation of Meth craving in male rats. Here we investigated projection-specific activation of afferent glutamate projections into DLS associated with incubated Meth seeking in female rats. We trained female rats to self-administer Meth (6-h/d for 10 d). On abstinence day 12, we injected cholera toxin subunit B (CTb, a retrograde tracer) unilaterally into DLS. On abstinence day 26, we tested rats for relapse to Meth seeking and measured Fos (a neuronal activity marker), and double-labeling of CTb and Fos in anterior cingulate cortex, anterior insula cortex, orbitofrontal cortex, basolateral amygdala, AIT, and parafascicular nuclei of thalamus. We observed neuronal activation in both cortical and thalamic regions associated with incubated Meth seeking. At the circuit level, AIT -> DLS projections were strongly activated, followed by other corticostriatal projections. Overall our results suggest that AIT to DLS may play a role in Meth seeking after prolonged abstinence in female rats.