Regional differences in striatal neuronal ensemble excitability following cocaine and extinction memory retrieval in Fos-GFP mice

Learned associations between drugs of abuse and the drug administration environment play an important role in addiction. In rodents, exposure to a drug-associated environment elicits conditioned psychomotor activation, which may be weakened following extinction learning. While widespread drug-induced changes in neuronal excitability have been observed, little is known about specific changes within neuronal ensembles activated during the recall of drugenvironment associations. Using a cocaine conditioned locomotion procedure, the present study assessed the excitability of neuronal ensembles in the nucleus accumbens core and shell (NAccore and NAcshell), and dorsal striatum (DS) following cocaine conditioning and extinction in Fos-GFP mice that express green fluorescent protein (GFP) in activated neurons (GFP+). During conditioning, mice received repeated cocaine injections (20 mg/kg) paired with a locomotor activity chamber (Paired) or home cage (Unpaired). 7-13 days later both groups were re-exposed to the activity chamber under drug-free conditions, and Paired, but not Unpaired, mice exhibited conditioned locomotion. In a separate group of mice, conditioned locomotion was extinguished by repeatedly exposing mice to the activity chamber under drugfree conditions. Following the expression and extinction of conditioned locomotion, GFP+ neurons in the NAccore (but not NAcshell and DS) displayed greater firing capacity compared to surrounding GFP– neurons. This difference in excitability was due to a generalized decrease in GFP– excitability following conditioned locomotion, and a selective increase in GFP+ excitability following its extinction. These results suggest a role for both widespread and ensemble-specific changes in neuronal excitability following recall of drug-environment associations.