Impulsivity and Addiction

Increased impulsivity is believed to contribute to the maintenance of addiction and the relapse to drug-seeking, and has been linked to hypofunction within the orbitofrontal cortex (OFC).  Little is known regarding the neurobiological mechanisms by which addictive drugs affect OFC function.  Our data indicate that cocaine self-administration in rats induces the transcription factor ΔFosB in the OFC which alters the effects of cocaine on impulsivity.  By combining self-administration with cognitive behavioural testing, we have recently been able to track the progressive decreases in motivation and impulse control associated with the development of habitual drug-taking.  Unlike with human subjects, it is possible to determine whether impulsivity predicts increased drug intake or whether prolonged exposure to cocaine causes changes in impulse control. We observed that rats develop tolerance to such disruptive effects of cocaine self-administration, but show a deficit in impulse control which is unmasked during withdrawal from drug.  Over-expression of ΔFosB within the OFC through viral-mediated gene transfer further impaired animals’ ability to regulate their drug intake and potentiated the increase in impulsivity observed during withdrawal.  Blocking the effects of ΔFosB in the OFC may therefore inhibit aspects of drug-seeking behaviour and attenuate the withdrawal-induced elevation in impulsive responding, and future research will aim to test this hypothesis.

It is increasingly recognized that pathological gambling (PG) shares many features with substance abuse, and that pathological gamblers likewise become dependent on the “rush” obtained from gambling. PG may therefore be regarded as a behavioural addiction, implying that therapeutic interventions that alleviate craving for drug may also reduce the desire to gamble.  The incidence of PG is also significantly higher in those with substance abuse disorder, and the co-occurrence of both conditions can have additive and detrimental effects on psychosocial functioning and the level of psychiatric distress experienced. Investigating the effects of drug addiction on risky decision-making would therefore provide valuable insight into PG and related disorders. We are planning to investigate these research questions using our new rodent models of gambling.

For more information, email info@winstanleylab.com with “Addiction” in the subject heading.