Intracranial self-stimulation in FAST and SLOW mice: effects of alcohol and cocaine

Abstract

Rationale Sensitivity to the stimulant and rewarding effects of alcohol may be genetically-correlated traits that predispose individuals to developing an alcohol use disorder. Objective 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. Methods 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 or BSR). 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. Results Alcohol dose-dependently lowered the threshold for self-stimulation (θ0) 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. Conclusions Selective breeding for alcohol locomotor stimulation also renders the mice more sensitive to the effects of alcohol, but not cocaine, on ICSS.

Adolescent intermittent ethanol exposure diminishes anhedonia during ethanol withdrawal in adulthood

“…The literature on brain reward function during ethanol intoxication is equivocal. While a number of studies, consistent with the present findings, report decreased (e.g., Schaefer & Michael, 1992) or unaltered brain reward function (e.g., Moolten & Kornetsky, 1990; Schaefer & Michael, 1987) by ethanol, other studies report ethanol-induced reward enhancement (e.g., Bain & Kornetsky, 1989; Bespalov et al, 1999; de Witte & Bada, 1983; Eiler et al, 2007; Fish et al, 2012; Lewis & June, 1990, 1994). Some of these discrepancies may be attributable to different experimental procedures.…”

“…Additionally, while the group mean data revealed no significant differences in the reward-enhancing effects of ethanol, exploratory analyses suggested that adolescent intermittent ethanol exposure may perhaps also increase sensitivity to the rewarding or appetitive effects of ethanol. Rodents selectively bred for high ethanol consumption show similar ethanol sensitivities (Chester et al, 2006; Eiler et al, 2007; Fish et al, 2012), suggesting that high sensitivity to ethanol reward and low sensitivity to ethanol withdrawal may predict heavy or problematic alcohol use.…”

“…Some of these discrepancies may be attributable to different experimental procedures. Enhanced brain reward function by acute ethanol in mice (e.g., Fish et al, 2012) and selectively bred alcohol-preferring rats (Eiler et al, 2007) may not generalize to outbred rat strains. Additionally, some studies used uncommon ICSS procedures (Lewis & June, 1990, 1994; Musgrave et al, 1989) or inferred reward enhancement from increased response rates (rate-frequency procedures; Bain & Kornetsky, 1989; de Witte & Bada, 1983).…”

“…However, the long-term effects of adolescent ethanol exposure on brain reward function during re-exposure to ethanol in adulthood have not been studied. Interestingly, rodent strains bred for high ethanol consumption exhibit heightened sensitivity to the reward-enhancing effects of ethanol and blunted sensitivity to the anhedonia associated with ethanol withdrawal (Chester et al, 2006; Eiler et al, 2007; Fish et al, 2012). These findings suggest that heightened sensitivity to the reward-enhancing effects of ethanol or blunted sensitivity to the anhedonia of ethanol withdrawal accompany and may predict increased ethanol consumption.…”

Effects of Acute and Repeated Administration of Oxycodone and Naloxone-Precipitated Withdrawal on Intracranial Self-Stimulation in Rats

“…First, Ewan and Martin used Fisher 344 rats, whereas this study used Sprague-Dawley rats. Strain differences can produce profound differences in drug effects in experimental assays including ICSS (Fish et al, 2012). Second, the previous study examined ICSS in the ventral tegmental area of the brain rather than the MFB.…”