Trait-like impulsivity does not predict escalation of heroin self-administration in the rat
- 637 Downloads
The neural and psychological mechanisms underlying vulnerability to drug addiction are poorly understood. Although a number of animal models have been developed to investigate vulnerability to stimulant addiction, few have considered how vulnerability traits such as impulsivity predict hallmark features of heroin addiction including the escalation of drug intake and increased propensity for relapse following protracted abstinence.
The aim of this study was to investigate whether high impulsivity in rats predicts the propensity to escalate intravenous heroin self-administration and to relapse following an extended withdrawal period from heroin.
High (HI)- and low (LI)-impulsive rats, defined by the extent of premature responding on the 5-choice serial reaction time test (5-CSRTT), were catheterized and allowed to self-administer heroin (40 μg/100 μl/infusion). After 5 days of short access (1 h/day) to heroin, rats were then given extended (6 h/day) access to heroin for 18 consecutive days.
High impulsivity predicted neither a greater tendency to acquire heroin SA nor an increased escalation of heroin self-administration. Moreover, high impulsivity was not associated with an increased propensity to relapse after protracted withdrawal from heroin. Nevertheless, marked inter-individual differences in the escalation of heroin self-administration were observed.
Although high impulsivity on the 5-CSRTT has been shown to predict loss of control over cocaine intake, this does not generalize to a loss of control over heroin self-administration. These findings suggest important distinctions in vulnerability mechanisms underlying cocaine and heroin addiction with trait-like impulsivity playing a role in stimulant but not opiate addiction.
KeywordsHeroin Intravenous self-administration Vulnerability Escalation Impulsivity Addiction Relapse
This work was supported by United Kingdom Medical Research Council (MRC) grants to BJE (G9536855) and JWD (G0701500) and by a European Communities Sixth Framework Programme Grant (‘Imagen’ LSHM-CT-2007-037286) and was conducted within the MRC/Wellcome Trust Behavioural and Clinical Neuroscience Institute. DB is supported by an INSERM AVENIR grant. The authors would like to thank Dr. Yavin Shaham for the insightful discussions.
Disclosure/Conflicts of interest
TWR discloses consultancy for Cambridge Cognition, Pfizer, Eli Lilly Inc., Wyeth, GlaxoSmithKline and Roche and holds share options in Cambridge Cognition and Allon Therapeutics. RMcN, JWD, BJE and DB have no disclosures.
- APA (2000) Diagnostic and statistical manual of mental disorders. APA, Washington DCGoogle Scholar
- Belin D, Everitt BJ (2008) Cocaine-Seeking Habits Depend upon Dopamine-Dependent Serial Connectivity Linking the Ventral with the Dorsal Striatum Neuron 57:432–441Google Scholar
- Dalley JW, Fryer T, Brichard L, Robinson E, Theobald D, Laane K, Pena Y, Murphy ER, 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 315:1267–1270CrossRefPubMedGoogle Scholar
- Ersche K, Turton AJ, Pradhan S, Bullmore ET, Robbins TW (2010) Drug addiction endophenotypes: impulsive versus sensation-seeking personality types. Biological Psychiatry, in pressGoogle Scholar