Intracranial self-stimulation in FAST and SLOW mice: effects of alcohol and cocaine
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Sensitivity to the stimulant and rewarding effects of alcohol may be genetically correlated traits that predispose individuals to develop an alcohol use disorder.
This study aimed to examine the effects of alcohol and cocaine on intracranial self-stimulation (ICSS) in FAST and SLOW mice, which were selectively bred for extremes in alcohol stimulation.
Male FAST and SLOW mice were conditioned to respond for reinforcement by direct electrical stimulation of the medial forebrain bundle (i.e., brain stimulation reward). ICSS responses were determined immediately before and after oral gavage with water or alcohol (0.3–2.4 g/kg) or intraperitoneal injection with saline or cocaine (1.0–30.0 mg/kg). In separate FAST and SLOW mice, the locomotor effects of these treatments were measured in activity chambers.
Alcohol dose-dependently lowered the threshold for self-stimulation (θ 0) and the frequency that maintained 50% of maximal responding (EF50) in FAST mice but did not significantly affect these parameters in SLOW mice. The largest effects of alcohol were after the 1.7- and 2.4-g/kg doses and were about 40% compared to water injection. Alcohol did not affect MAX response rates, but dose-dependently stimulated locomotor activity in FAST mice. Cocaine lowered thresholds equally in FAST and SLOW mice, although cocaine-stimulated locomotor activity was higher in the FAST than in the SLOW mice.
Selective breeding for alcohol locomotor stimulation also renders the mice more sensitive to the effects of alcohol, but not cocaine, on ICSS.
KeywordsEthanol Locomotion Psychostimulant Dopamine Genetics Brain stimulation reward
The authors acknowledge the following support for this research: grants AA 018335 to CJM, AA007573 to the Bowles Center of Alcohol Studies and funding from the Department of Veterans Affairs, and NIAAA P60 AA010760 to TJP. The authors are indebted to Megan McGuigan for facilitating the transfer of mice from the Portland VA to the UNC animal facility, Kelly Psilos for her assistance with histology, Dr. Sara Faccidomo for technical assistance with the activity monitors, and Dr. Sarah Holstein for her helpful comments and observations regarding the FAST/SLOW phenotype.
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