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Abstract
Previous studies using a rat 5-choice serial reaction time task have established a critical role for dopamine D2 receptors in regulating increments in motor impulsivity induced by acute administration of the psychostimulant drugs amphetamine and nicotine. Here we investigated whether cannabinoid CB1 and/or μ-opioid receptors are involved in nicotine-induced impulsivity, given recent findings indicating that both receptor systems mediate amphetamine-induced motor impulsivity. Results showed that the cannabinoid CB1 receptor antagonist SR141716A, but not the opioid receptor antagonist naloxone, reduced nicotine-induced premature responding, indicating that nicotine-induced motor impulsivity is cannabinoid, but not opioid receptor-dependent. In contrast, SR141716A did not affect impulsivity following a challenge with the dopamine transporter inhibitor GBR 12909, a form of drug-induced impulsivity that was previously found to be dependent on μ-opioid receptor activation. Together, these data are consistent with the idea that the endogenous cannabinoid, dopamine, and opioid systems each play important, but distinct roles in regulating (drug-induced) motor impulsivity. The rather complex interplay between these neurotransmitter systems modulating impulsivity will be discussed in terms of the differential involvement of mesocortical and mesolimbic neurocircuitry.
Highlights
Impulsivity is a multifaceted construct covering various, largely independent, behavioral measures including inhibitory control or motor impulsivity, i.e., the inability to restrain inappropriate behavior (Evenden, 1999; Winstanley et al, 2006; Pattij and Vanderschuren, 2008; Broos et al, 2012)
We determined whether CB1 receptor activation plays a role in nicotine-induced motor impulsivity by examining the effects of the selective cannabinoid CB1 receptor antagonist SR141716A (K i values of 1.8– 12.3 and 514–13200 nM for respectively cannabinoid CB1 and CB2 receptors; Pertwee, 2010) pretreatment on nicotine-induced impulsivity in the 5choice serial reaction time task (5-CSRTT)
SR141716A alone did not affect premature responding at any dose, thereby contrasting an initial study on the effects of this compound on premature responding in rats (Pattij et al, 2007a)
Summary
Impulsivity is a multifaceted construct covering various, largely independent, behavioral measures including inhibitory control or motor impulsivity, i.e., the inability to restrain inappropriate behavior (Evenden, 1999; Winstanley et al, 2006; Pattij and Vanderschuren, 2008; Broos et al, 2012). A common effect of acute administration of addictive substances such as psychostimulants, opiates, and alcohol in rodents is an increase in motor impulsivity (Cole and Robbins, 1987; van Gaalen et al, 2006; Olmstead et al, 2009; Pattij et al, 2009), reflected in an increase in premature responding in, e.g., the 5choice serial reaction time task (5-CSRTT; Robbins, 2002) This commonality between different types of drugs of abuse may be related to their shared ability to increase dopamine release in the brain (Di Chiara and Imperato, 1988; Sulzer, 2011). Most studies on amphetamine-induced motor impulsivity revealed an important role for the mesolimbic dopamine system, and dopamine signaling and dopamine D2 receptor activity in the nucleus accumbens (Cole and Robbins, 1987, 1989; Pattij et al, 2007b)
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