Previous work has demonstrated that immediately following 21 days of self-administration, while blood levels of cocaine are still high, there are reductions in functional activity in a number of brain regions (Macey et al., 2004); however, the question remained as to whether these changes persisted beyond the self-administration session. Most functional activity studies determine the effects of a drug challenge; however, the present study focused on rates of local cerebral glucose utilization selleck compound in the absence of drug, to determine
its residual effects. These data are important because determining the persistent effects of cocaine self-administration on functional activity can point to changes in specific brain regions and circuits which may be predictive of behavioral deficits in cocaine-addicted individuals. We show that cocaine self-administration results in functional reductions in brain regions involved in reward, learning and memory that are present 48 h after the final cocaine session. We also see reduced function of the dorsal raphe and locus coeruleus, which has implications for global brain function as
these nuclei have an extensive network of projections. learn more Using behavioral activity analysis after cocaine self-administration we report alterations which could be predicted based on decreased serotonergic and dopaminergic functioning, demonstrating that these neural changes have behavioral implications. The SB-3CT reduced functional activity in selected regions suggests that even limited cocaine self-administration is capable of producing reductions in regional brain activity that
may have adverse consequences for normal functioning. Male, Sprague-Dawley rats (375–400 g; Harlan Laboratories, Frederick, MD, USA) were maintained according to the National Institutes of Health guidelines in Association for Assessment and Accreditation of Laboratory Animal Care-accredited facilities. The experimental protocol was approved by the Institutional Animal Care and Use Committee at Wake Forest School of Medicine. Rats (n = 14) were anesthetized with ketamine (100 mg/kg) and xylazine (10 mg/kg), implanted with chronic indwelling jugular catheters, and trained for i.v. self-administration as previously described (Liu et al., 2005). Following surgery, animals were singly housed, and all self-administration sessions took place in the home cage. Each animal was maintained on a reverse light cycle (03:00 h lights off; 15:00 h lights on), and all self-administration procedures occurred during the active/dark cycle. Sessions were 6 h in length and were terminated at the end of the 6 h or after 40 injections of drug. Animals self-administered cocaine (1.5 mg/kg per injection over 4 s) on a fixed-ratio 1 schedule of administration. Concurrent with the start of each injection, the lever retracted and a stimulus light was activated for 20 s to signal a time-out period.