Repeated Cocaine Self-Administration Alters Processing of Cocaine-Related Information in Rat Prefrontal Cortex

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Abstract
One of the core symptoms of cocaine addiction is compulsive drug-seeking behavior. Although the precise neural substrates are unknown, it has been hypothesized that this behavior involves cocaine-induced hypofunction of the prefrontal cortex (PFC) or “hypofrontality.” To test this hypothesis, PFC neuronal activity was monitored in rats during ∼3 weeks of cocaine self-administration (SA). Rats were trained to press a lever to self-administer cocaine in daily 2 h sessions. Responding was reinforced contingent on a modified fixed-ratio 5 schedule of reinforcement. In the first SA session, the overall firing rate and burst rate were significantly decreased after cocaine infusions relative to the period immediately before the session. These effects disappeared after ≥10 d of drug SA and were replaced by a significant increase in burst duration and firing rate within a burst. Notably, however, the level of basal activity before the first drug infusion of each SA session decreased significantly after multiple weeks of cocaine exposure. Collectively, these data support the view that although repeated sessions of cocaine SA decrease basal PFC activity, increased burst-related firing in response to cocaine infusions suggests that processing of cocaine-related information is enhanced and may contribute to increased control by cocaine over cocaine-seeking behavior.