High anxiety is a predisposing endophenotype for loss of control over cocaine, but not heroin, self-administration in rats
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Although high anxiety is commonly associated with drug addiction, its causal role in this disorder is unclear.
In light of strong evidence for dissociable neural mechanisms underlying heroin and cocaine addiction, the present study investigated whether high anxiety predicts the propensity of rats to lose control over intravenous cocaine or heroin self-administration.
Sixty-four rats were assessed for anxiety in the elevated plus-maze, prior to extended access to intravenous cocaine or heroin self-administration.
High-anxious rats, identified in the lower quartile of the population, showed a greater escalation of cocaine, but not heroin, self-administration compared with low-anxious rats selected in the upper quartile of the population. Anxiety scores were also positively correlated with the extent of escalation of cocaine self-administration.
The present data suggest that high anxiety predisposes rats to lose control over cocaine—but not heroin—intake. High anxiety may therefore be a vulnerability trait for the escalation of stimulant but not opiate self-administration.
KeywordsAddiction Anxiety Cocaine Escalation Heroin Self-administration
This work was supported by the United Kingdom Medical Research Council (Grant 9536855 to BJE and Grant G0701500 to JWD) and was conducted within the MRC/Wellcome Trust Behavioural and Clinical Neuroscience Institute. RD was financially supported by a Young Foreign Researcher grant from the University of Poitiers. DB is supported by an INSERM AVENIR grant.
The authors report no competing interests.
DB and BJE were responsible for the study concept. RD, BJE, JWD and DB designed the experiments. RD, YP, ACM and AM performed the experiments. RD and DB performed statistical analyses and designed the figures. RD drafted the manuscript. DB, BJE, JWD and TWR provided critical revision of the manuscript for important intellectual content. All authors critically reviewed content and approved final version for publication.
- APA (2000) Diagnostic and statistical manual of mental Disorders fourth edition, text revision (DSM-IV TR). American Psychiatric Association, WashingtonGoogle Scholar
- Cruz FC, Quadros IM, Hogenelst K, Planeta CS, Miczek KA (2011) Social defeat stress in rats: escalation of cocaine and “speedball” binge self-administration, but not heroin. Psychopharmacology (Berl) 215:165-175Google Scholar
- Dalley JW, Fryer T, Brichard L, Robinson E, Theobald DE, Laane K, Pena Y, Murphy E, Shah Y, Probst K, Abakumova I, Aigbirhio F, Richards H, Hong Y, Baron J, Everitt BJ, Robbins TW (2007) Nucleus accumbens d2/3 receptors predict trait impulsivity and cocaine reinforcement. Science 315(5816):1267–1270PubMedCrossRefGoogle Scholar
- Homberg JR, van den Akker M, Raaso HS, Wardeh G, Binnekade R, Schoffelmeer AN, de Vries TJ (2002) Enhanced motivation to self-administer cocaine is predicted by self-grooming behaviour and relates to dopamine release in the rat medial prefrontal cortex and amygdala. Eur J Neurosci 15(9):1542–1550PubMedCrossRefGoogle Scholar
- Lejuez CW, Paulson A, Daughters SB, Bornovalova MA, Zvolensky MJ (2006). The association between heroin use and anxiety sensitivity among inner-city individuals in residential drug use treatment. Behav Res Ther 44(5), 5, 667–677Google Scholar
- Molander AC, Mar A, Norbury A, Steventon S, Moreno M, Caprioli D, Theobald DE, Belin D, Everitt BJ, Robbins TW, Dalley JW (2011) High impulsivity predicting vulnerability to cocaine addiction in rats: some relationship with novelty preference but not novelty reactivity, anxiety or stress. Psychopharmacology (Berl) 215(4):721–731CrossRefGoogle Scholar
- Norton GR (2001) Substance use/abuse and anxiety sensitivity what are the relationships? Addict Behav 26:935-946Google Scholar