Nicholas J. Grahame

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Much evidence from studies in humans and animals supports the hypothesis that alcohol addiction is a complex disease with both hereditary and environmental influences. Molecular determinants of excessive alcohol consumption are difficult to study in humans. However, several rodent models show a high or low degree of alcohol preference, which provides a(More)
High and low alcohol preference (HAP and LAP, respectively) mice were created by 10 generations of bidirectional selection for differences in two-bottle choice alcohol consumption. The progenitors used for selection were HS/lbg mice, which are a genetically defined, outbred stock. During selection, mice had 24-h, daily access to 10% alcohol (v/v) and water(More)
BACKGROUND Repeated studies have shown that high impulsivity, when defined as the tendency to choose small immediate rewards over larger delayed rewards, is more prevalent in drug addicts and alcoholics when compared with nonaddicts. Assessing whether impulsivity precedes and potentially causes addiction disorders is difficult in humans because they all(More)
The effect of the dopamine receptor antagonist haloperidol on the development of sensitization to ethanol-induced increases in locomotor activity was examined in DBA/2J mice. In Experiment 1, different groups of mice were given saline or ethanol (2 g/kg) immediately before each of four locomotor activity sessions (48-h intervals), and 1 h after pretreatment(More)
The Rescorla-Wagner model has been the most influential theory of associative learning to emerge from the study of animal behavior over the last 25 years. Recently, equivalence to this model has become a benchmark in assessing connectionist models, with such equivalence often achieved by incorporating the Widrow-Hoff delta rule. This article presents the(More)
Rationale: Some theories have advanced a role for both locomotor sensitization and tolerance in the reinforcing properties of drugs. The present studies used selected lines of mice to assess genetic correla- tions among ethanol drinking, ethanol locomotor sensitization, and tolerance to the depressant effects of ethanol. Objectives: Ethanol-naive high- and(More)
BACKGROUND Selection studies and genetic analyses of drinking behavior in rodents often involved unlimited access to alcohol over a period of weeks, with water and food freely available. Most studies investigating the pharmacology of alcohol drinking, on the other hand, use procedures in which access to alcohol is limited to a particular time each day.(More)
BACKGROUND Impulsivity is genetically correlated with, and precedes, addictive behaviors and alcoholism. If impulsivity or attention is causally related to addiction, certain pharmacological manipulations of impulsivity and/or attention may affect alcohol drinking, and vice versa. The current studies were designed to explore the relationship among(More)
Development of procedures yielding substantial blood alcohol concentrations during voluntary access to an alcohol solution in mice is necessary to further characterize genetic and neurobiologic mechanisms underlying alcohol self-administration. Although, in experimental situations, some populations of mice readily drink an alcohol solution, results from(More)
In experiment 1, two different strains of mice [C57BL/6J (B6) and DBA/2J (D2)] were allowed to nosepoke for 5 µl intravenous (IV) infusions during 2-h daily sessions. Two nosepoke holes were available, only one of which was reinforced on an FR-3 schedule with a 10-s time-out indicated by a light inside the reinforced nosepoke hole. During the first nine(More)