Coffey, Kevin R.. A longitudinal analysis of medium spiny neuron activity in dorsolateral striatum during chronic cocaine self-administration. Retrieved from https://doi.org/doi:10.7282/T3QC01TK
DescriptionSubstance abuse is defined by continued consumption of drugs despite their negative consequences, and its treatment is plagued by exceptionally high relapse rates (40-60%). Current behavioral and neurobiological theories of substance abuse predict that with chronic use, drug consumption becomes habitual and neural activity shifts from the nucleus accumbens (NAc) to the dorsolateral Striatum (DLS). In the present study, we sought to test the latter theory: that in the course of chronic cocaine self-administration, DLS neurons acquire phasic patterns of firing in relation to drug-taking behaviors. We recorded from single body part (SBP) neurons in DLS that are specifically related to vertical head movement, (i.e. neck or head sensitive neurons) as well as a control group of non-SBP neurons. Animals self-administered cocaine using a vertical head movement operant and exhibited behavioral evidence of skilled self-administration. To analyze changes in neural firing rate (FR) across cocaine self-administration, we developed a custom generalized mixed model (2x2x12) with 2 levels of Neuron Type (Head Movement and Control), 2 levels of Firing Type (Phasic and Baseline) and 12 levels of recording Session. Baseline (non-movement) FR decreased in DLS neurons across days, but this decrease was confined to Head Movement neurons. Phasic (during head movements) FR differed significantly across sessions in both Head Movement and Control neurons. However, Phasic FR was significantly greater than Baseline FR only in Head Movement neurons, during the first two weeks (Days 3-4, 9-10, and 11-12). In the last two weeks, the population of Head Movement neurons in DLS contributed less to drug-taking behavior. Inconsistent with the tested theory, DLS does not become globally more active with chronic cocaine SA. Instead, chronic cocaine self-administration is related to a decrease in DLS activity, specifically in neurons that process the skill required for self-administering. Consistent with the tested hypothesis however, a small number of neurons acquired progressively more robust head movement activity after 24+ days of self-administration. During abstinence, these neurons could be responsible for processing or executing relapse behaviors.