Genetics of novelty seeking, amphetamine self‐administration and reinstatement using inbred rats

Previous research using outbred rats indicates that individual differences in activity in a novel environment predict sensitivity to the reinforcing effect of psychostimulant drugs. The current study examined if the link between responses related to novelty and amphetamine self‐administration is heritable. Twelve inbred rat strains were assessed for locomotor activity in a novel environment, preference for a novel environment, and intravenous amphetamine self‐administration (acquisition, extinction and amphetamine‐induced reinstatement). Strain differences were observed in activity in a novel environment, novelty preference and amphetamine self‐administration, indicating a genetic influence for each of these behaviors. While there was no relation between activity in an inescapable novel environment and amphetamine self‐administration, strain‐dependent differences in novelty preference were positively correlated with the amount of amphetamine self‐administered. There was also a positive correlation between the dose‐dependent rate of amphetamine self‐administration and magnitude of reinstatement. These results show that the activity in an inescapable novel environment and the preference for a novel environment are different genetically, and thus likely to reflect different behavioral constructs. Moreover, these results implicate a genetic influence on the relation between novelty seeking and stimulant self‐administration, as well as on the relation between stimulant reward and reinstatement.

[1]  L. Fattore,et al.  The Roman High- and Low-Avoidance Rat Lines Differ in the Acquisition, Maintenance, Extinction, and Reinstatement of Intravenous Cocaine Self-Administration , 2009, Neuropsychopharmacology.

[2]  J. Javitch,et al.  Amphetamine and Methamphetamine Differentially Affect Dopamine Transporters in Vitro and in Vivo* , 2009, Journal of Biological Chemistry.

[3]  H. Akil,et al.  The effects of novelty-seeking phenotypes and sex differences on acquisition of cocaine self-administration in selectively bred High-Responder and Low-Responder rats , 2008, Pharmacology Biochemistry and Behavior.

[4]  M. Bardo,et al.  Individual Differences in Amphetamine Self-Administration: The Role of the Central Nucleus of the Amygdala , 2008, Neuropsychopharmacology.

[5]  J. Crabbe,et al.  Drug reward and intake in lines of mice selectively bred for divergent exploration of a hole board apparatus , 2007, Genes, brain, and behavior.

[6]  N. Zahniser,et al.  Inbred Lewis and Fischer 344 rat strains differ not only in novelty- and amphetamine-induced behaviors, but also in dopamine transporter activity in vivo , 2007, Brain Research.

[7]  X. Zhang,et al.  Strain differences in maintenance of cocaine self-administration and their relationship to novelty activity responses. , 2007, Behavioral neuroscience.

[8]  David H. Epstein,et al.  Toward a model of drug relapse: an assessment of the validity of the reinstatement procedure , 2006, Psychopharmacology.

[9]  J. Crabbe,et al.  Genetic independence of mouse measures of some aspects of novelty seeking , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[10]  M. Bardo,et al.  Novelty seeking and drug use: contribution of an animal model. , 2005, Experimental and clinical psychopharmacology.

[11]  M. Marinelli.  The many facets of the locomotor response to a novel environment test: theoretical comment on Mitchell, Cunningham, and Mark (2005). , 2005, Behavioral neuroscience.

[12]  Jennifer M. Mitchell,et al.  Locomotor activity predicts acquisition of self-administration behavior but not cocaine intake. , 2005, Behavioral neuroscience.

[13]  J. Crabbe,et al.  An analysis of the genetics of alcohol intoxication in inbred mice , 2005, Neuroscience & Biobehavioral Reviews.

[14]  M. Bardo,et al.  The effect of novelty on amphetamine self-administration in rats classified as high and low responders , 2004, Psychopharmacology.

[15]  S. Higgins,et al.  Erratum to The validity of the reinstatement model of craving and relapse to drug use , 2003, Psychopharmacology.

[16]  S. Higgins,et al.  The validity of the reinstatement model of craving and relapse to drug use , 2003, Psychopharmacology.

[17]  T. Kosten,et al.  HPA axis function and drug addictive behaviors: insights from studies with Lewis and Fischer 344 inbred rats , 2002, Psychoneuroendocrinology.

[18]  P. Vezina,et al.  Locomotor response to novelty predicts a rat's propensity to self-administer nicotine , 2001, Psychopharmacology.

[19]  M. Kreek,et al.  Predictable individual differences in the initiation of cocaine self-administration by rats under extended-access conditions are dose-dependent , 2001, Psychopharmacology.

[20]  M. Carroll,et al.  Regulation of drug intake. , 2001, Experimental and clinical psychopharmacology.

[21]  A. Norman,et al.  Satiety threshold: a quantitative model of maintained cocaine self-administration , 1999, Brain Research.

[22]  M. Bardo,et al.  Individual differences in novelty-induced activity and the rewarding effects of novelty and amphetamine in rats , 1998, Behavioural Processes.

[23]  F. Chaouloff,et al.  A multiple-test study of anxiety-related behaviours in six inbred rat strains , 1997, Behavioural Brain Research.

[24]  R. Luedtke,et al.  Variations in cocaine self-administration by inbred rat strains under a progressive-ratio schedule , 1996, Psychopharmacology.

[25]  R. Frankham.  Introduction to quantitative genetics (4th edn): by Douglas S. Falconer and Trudy F.C. Mackay Longman, 1996. £24.99 pbk (xv and 464 pages) ISBN 0582 24302 5 , 1996 .

[26]  M. Bardo,et al.  Psychobiology of novelty seeking and drug seeking behavior , 1996, Behavioural Brain Research.

[27]  J. Crabbe,et al.  Type I and type II error rates for quantitative trait loci (QTL) mapping studies using recombinant inbred mouse strains , 1996, Behavior genetics.

[28]  M. Zuckerman.  Behavioral Expressions and Biosocial Bases of Sensation Seeking , 1994 .

[29]  J. Crabbe,et al.  Genetic determinants of sensitivity to ethanol in inbred mice. , 1994, Behavioral neuroscience.

[30]  D. Clark,et al.  Behaviour in the novel environment predicts responsiveness to d‐amphetamine in the rat: a multivariate approach , 1993, Behavioural pharmacology.

[31]  R. Messing,et al.  Food deprivation enhances both autoshaping and autoshaping impairment by a latent inhibition procedure , 1991, Behavioural Processes.

[32]  M. Le Moal,et al.  Factors that predict individual vulnerability to amphetamine self-administration. , 1989, Science.

[33]  C. Robert Cloninger,et al.  Neurogenetic adaptive mechanisms in alcoholism. , 1987, Science.

[34]  J. P. Hegmann,et al.  Estimating genetic correlations from inbred strains , 1981, Behavior genetics.

[35]  H. Grüneberg,et al.  Introduction to quantitative genetics , 1960 .

[36]  M. Carroll,et al.  Autoshaping i.v. cocaine self-administration in rats: effects of nondrug alternative reinforcers on acquisition , 2005, Psychopharmacology.

[37]  S. Dworkin,et al.  Self-administration of drugs of abuse , 2002 .

[38]  D. Falconer.  Introduction to quantitative genetics. 1. ed. , 1984 .

[39]  C. Schuster.  Self-Administration of Drugs , 1973 .