Impulsivity predicts the escalation of cocaine self-administration in rats

Abstract

Impulsivity, as measured by the delay-discounting task, predicts the acquisition of cocaine selfadministration and reinstatement of cocaine seeking in rats. The purpose of this study was to extend these results to the escalation phase of drug self-administration. Female rats were initially screened for high (HiI) or low (LoI) impulsivity for food reinforcement using a delay-discounting procedure. They were then implanted with i.v. catheters and trained to lever press for cocaine infusions (0.8 mg/ kg). Once cocaine intake stabilized, rats were allowed to self-administer cocaine (0.4 mg/kg) under a fixed-ratio 1 (FR 1) schedule during 3, 2 hr short-access sessions. Subsequently, performance was briefly assessed under a progressive ratio (PR) schedule for 3 doses of cocaine (0.2, 0.8, and 3.2 mg/ kg). Following PR testing, the cocaine dose was then changed to 0.4 mg/kg. Session length was then extended to 6-hr for 21 days (extended access), and 0.4 mg/kg cocaine was available under a FR 1 schedule. After the 21-day extended access phase, responses and infusions under the short access and PR dose-response conditions were reassessed. The results indicated that HiI rats escalated cocaine-reinforced responding during the extended access condition, but LoI rats did not. HiI rats also earned significantly more infusions than LoI rats under the post-escalation short-access condition. However, HiI and LoI rats did not differ under the pre-and post-extended access PR conditions. This study suggests that individual differences in impulsivity predict escalation of cocaine self-administration in female rats, which may have implications in the prediction of binge-like patterns of cocaine intake in women.

Adolescent Risk Taking, Cocaine Self-Administration, and Striatal Dopamine Signaling

“…Adolescents who display greater impulsivity, risk taking, and sensation seeking display concomitantly greater rates of substance use (Chambers et al, 2003;Spear, 2000), and studies in adult rats show that measures of both impulsive action and impulsive choice predict cocaine SA (Dalley et al, 2007;Perry et al, 2005;Perry et al, 2008). In Experiment 1, risk taking predicted cocaine SA only during the acquisition and not the maintenance period, whereas impulsivity measures are reported to predict acquisition as well as measures of compulsive-like cocaine SA that are more closely linked to addiction (Anker et al, 2009;Belin et al, 2008;Broos et al, 2012;Deroche-Gamonet et al, 2004;Perry et al, 2005;Perry et al, 2008;Vanderschuren and Everitt, 2004). The absence of relationships between risk taking and cocaine intake during maintenance could be due to the fact that SA under such conditions is reportedly not strongly tied to compulsive-like cocaine intake (Belin et al, 2008).…”

“…In particular, because predispositions for drug use can be evident in human adolescence (Chambers et al, 2003;Chartier et al, 2010), the ability to capture a predictive phenotype at this stage of development is important for modeling vulnerability to drug use. However, it is also notable that several other adult rodent models of addiction-associated phenotypes, particularly those related to impulsive behavior, predict aspects of cocaine SA that are more closely linked to addiction than acquisition (eg, enhanced motivation to selfadminister, resistance to extinction; Anker et al, 2009;Belin et al, 2008;Dalley et al, 2007;Perry et al, 2005). The extent to which elevated risk taking predicts such 'addiction-like' elements of SA behavior remains to be determined; however, the fact that low levels of ventral striatal D2/3 receptor availability are associated with compulsive cocaine intake in other models (Dalley et al, 2007) suggests that such predictive relationships may be evident with risk taking as well.…”

“…Animal models have provided considerable insight into the nature and direction of relationships between some maladaptive behaviors and drug use. For example, high levels of impulsive choice predict both acquisition and escalation of cocaine self-administration, which in turn can cause increases in impulsive choice (Anker et al, 2009;Mendez et al, 2010;Perry et al, 2008;Setlow et al, 2009). There is less known, however, regarding relationships between risk taking and drug use, particularly in the context of adolescence.…”

Individual Differences and Social Influences on the Neurobehavioral Pharmacology of Abused Drugs

“…A comprehensive coverage of these tasks is provided in several excellent reviews (Evenden, 1999;Winstanley et al, 2010;Dalley et al, 2011). It is important to note that there is little relation in performance among these various tasks (Anker et al, 2009;Marusich et al, 2011), suggesting that each task measures a different facet of impulsivity. One nomenclature is to parse impulsivity tasks into three broad categories: 1) impulsive choice, which is primarily decision making when choosing between a small immediate reward and a larger delayed reward; 2) impulsive action, which is primarily motoric; and 3) impulsive reflection, which is premature responding before adequate sensory processing (Dalley et al, 2011).…”

“…Perhaps the best example is the delay discounting task, which allows animals to choose between an immediate small reward and a delayed large reward, with impulsivity being defined as a preference for the small immediate reward (Rodriguez and Logue, 1988). When screened initially on delay discounting, rats that are high in impulsivity show faster acquisition, escalation, and reinstatement of selfadministration with cocaine (Perry et al, 2005Anker et al, 2009), methylphenidate (Marusich and Bardo, 2009), nicotine (Diergaarde et al, 2008, morphine (Garcia-Lecumberri et al, 2011), and alcohol (Poulos et al, 1995). The predictive effect of delay discounting generalizes to amphetamine CPP (Yates et al, 2012), indicating that lever pressing is not a prerequisite to show a relation between individual differences in impulsive choice and drug reward.…”