Individual differences in behavior, neurochemistry and pharmacology associated with voluntary alcohol intake

Abstract: Alcohol use disorder is a worldwide public health problem and is a disorder with substantial individual variation. There are suggested links between various behavioral traits, comorbid psychiatric diseases and excessive alcohol consumption. Moreover, the endogenous opioid system is involved in alcohol reward and reinforcement, and implicated in the action of alcohol. However, less is known about the complex associations between individual differences in behavior, alcohol consumption, pharmacotherapy response and related neurochemical mechanisms. Experimental animal models are critical for understanding the neurobiological underpinnings of alcohol use disorder.The overall aims of this thesis were: i) to study the association between behavior and voluntary alcohol intake in outbred rats; ii) to study the association of voluntary alcohol intake, behavior, opioid receptor density and response to naltrexone; and iii) to obtain detailed behavioral characterizations of the animals on the basis of their voluntary alcohol intake.The results revealed that the multivariate concentric square fieldTM (MCSF) test was a complementary method for understanding mechanisms underlying various mental states. The MCSF broadened the perspective on risk-related behaviors, including aspects of risk assessment. Individual differences in alcohol intake using the modified intermittent access paradigm enabled analyses of drinking patterns in high and low alcohol-drinking rats. There was an alcohol deprivation effect in high-drinking animals only. The behavior profiling of high alcohol drinking- rats before and after alcohol access suggested that this subgroup was consuming alcohol for its anxiolytic properties. Long-lasting changes were found in the mu and the delta opioid receptors after long-term, intermittent voluntary alcohol intake; some of these changes are in line with findings in humans. The voluntary alcohol consumption and the concomitant response to naltrexone were different for Wistar rats from different suppliers. Moreover, the Rcc Wistar rats may be more suitable for studies of alcohol use disorders due to increasing alcohol intake and the presence of a high-drinking subpopulation with increasing alcohol intake over time. The high-drinking subpopulation showed pronounced effects of naltrexone on alcohol intake.In conclusion, studies of individual differences increase understanding of variability in behavior, pharmacotherapy response and factors involved in vulnerability of alcohol use disorders.