Sai Manikandan

Methamphetamine self-administration in mice does not affect the dendritic anatomy of direct pathway spiny projection neurons in the dorsolateral striatum

Methamphetamine(meth) is an addictive psychostimulant that increases levels of synaptic monoamine neurotransmitters, particularly dopamine. The dorsolateral striatum (DLS) is densely innervated by substantia nigra pars compacta (SNc) dopamine neurons and clinical evidence suggests that levels of dopamine in the dorsal striatum may correlate with levels of craving in cocaine abusers. Preclinical studies also implicated the DLS in maladaptive drug-seeking behavior, including meth-seeking. This compulsive maladaptive seeking behavior is a hallmark of substance use disorders and is a primary impediment to maintaining abstinence. Despite evidence identifying the DLS as an important region involved in substance use disorders, neuronal dysfunction in this region that may contribute to maladaptive seeking is understudied and studies examining effects of meth are particularly scarce. The DLS is primarily comprised of GABAergic spiny projection neurons, which can be subdivided into D2 receptor expressing indirect pathway (iSPN) and D1 receptor expressing direct pathway (dSPN) spiny projection neurons, both of which receive dopaminergic input from the substantia nigra pars compacta. The goal of this project was to examine neuronal function and dendritic anatomy of SPNs after acute and protracted abstinence from meth using a mouse model of intravenous self-administration. During acute abstinence dSPN neuron excitability was increased and was associated with a decreased afterhyperpolarization amplitude but after protracted abstinence excitability and the afterhyperpolarization amplitude was normalized; iSPNs however were unaffected at both acute and protracted abstinence. Dendritic anatomy of dSPNs and iSPNs was also analyzed and was unaffected in both neuronal populations at acute and protracted abstinence.