Decreased Reward Sensitivity in Rats from the Fischer344 Strain Compared to Wistar Rats Is Paralleled by Differences in Endocannabinoid Signaling

BACKGROUND: The aim of the present study was to examine if differences in the endocannabinoid (ECB) system might be linked to strain specific variations in reward-related behavior in Fischer344 (Fischer) and Wistar rats. METHODOLOGY/PRINCIPAL FINDINGS: Two rat strains, the Fischer and the Wistar strain, were tested for different aspects of reward sensitivity for a palatable food reward (sweetened condensed milk, SCM) in a limited-access intake test, a progressive ratio (PR) schedule and the pleasure-attenuated startle (PAS) paradigm. Additionally, basic differences in the ECB system and cannabinoid pharmacology were examined in both rat strains. Fischer rats were found to express lower reward sensitivity towards SCM compared to Wistar rats. These differences were observed for consummatory, motivational and hedonic aspects of the palatable food reward. Western blot analysis for the CB1 receptor and the ECB degrading enzyme fatty acid amide hydrolase (FAAH) revealed a lower expression of both proteins in the hippocampus (HPC) of Fischer rats compared to the Wistar strain. Furthermore, increased cannabinoid-stimulated extracellular-regulated kinase (ERK) phosphorylation was detected in Wistar rats compared to the Fischer strain, indicating alterations in ECB signaling. These findings were further supported by the pharmacological results, where Fischer rats were found to be less sensitive towards the effects of the CB1 receptor antagonist/inverse agonist SR141716 and the cannabinoid agonist WIN 55,212-2. CONCLUSIONS/SIGNIFICANCE: Our present findings indicate differences in the expression of the CB1 receptor and FAAH, as well as the activation of ECB signaling pathways between Fischer and Wistar rats. These basic differences in the ECB system might contribute to the pronounced differences observed in reward sensitivity between both rat strains

Enhanced Incentive Motivation for Sucrose-Paired Cues in Adolescent Rats: Possible Roles for Dopamine and Opioid Systems

Vulnerability to the effects of drugs of abuse during adolescence may be related to altered incentive motivation, a process believed to be important in addiction. Incentive motivation can be seen when a neutral stimulus acquires motivational properties through repeated association with a primary reinforcer. We compared adolescent (postnatal day (PND) 24–50) and adult (>PND 70) rats on a measure of incentive motivation: responding for a conditioned reinforcer (CR). Rats learned to associate the delivery of 0.1 ml of 10% sucrose with a conditioned stimulus (CS; light and tone); 30 pairings per day were given over 14 days. Then, we measured responding on a lever delivering the CS (now a CR) after injections of amphetamine (0, 0.25 or 0.5 mg/kg). We also examined responding for CR when the CS and sucrose were paired or unpaired during conditioning, and responding for the primary reinforcer (10% sucrose) in control experiments. Finally, we examined the effects of D1 and D2 dopamine receptor antagonists (SCH 39166 and eticlopride, respectively) and an opioid receptor antagonist (naltrexone) on responding for a CR in adolescent rats. Adolescents but not adults acquired responding for a CR, but adolescents responded less than adults for the primary reinforcer. Responding for a CR depended upon the pairing of the CS and sucrose during conditioning. Both dopamine and opioid receptor antagonists reduced responding for the CR. Therefore, incentive motivation may be enhanced in adolescents compared with adults, and incentive motivation may be mediated in part by both dopamine and opioid systems

Determinants of Early Alcohol Use In Healthy Adolescents: The Differential Contribution of Neuroimaging and Psychological Factors

Individual variation in reward sensitivity may have an important role in early substance use and subsequent development of substance abuse. This may be especially important during adolescence, a transition period marked by approach behavior and a propensity toward risk taking, novelty seeking and alteration of the social landscape. However, little is known about the relative contribution of personality, behavior, and brain responses for prediction of alcohol use in adolescents. In this study, we applied factor analyses and structural equation modeling to reward-related brain responses assessed by functional magnetic resonance imaging during a monetary incentive delay task. In addition, novelty seeking, sensation seeking, impulsivity, extraversion, and behavioral measures of risk taking were entered as predictors of early onset of drinking in a sample of 14-year-old healthy adolescents (N=324). Reward-associated behavior, personality, and brain responses all contributed to alcohol intake with personality explaining a higher proportion of the variance than behavior and brain responses. When only the ventral striatum was used, a small non-significant contribution to the prediction of early alcohol use was found. These data suggest that the role of reward-related brain activation may be more important in addiction than initiation of early drinking, where personality traits and reward-related behaviors were more significant. With up to 26% of explained variance, the interrelation of reward-related personality traits, behavior, and neural response patterns may convey risk for later alcohol abuse in adolescence, and thus may be identified as a vulnerability factor for the development of substance use disorders