On the Role of Cannabinoid CB1- and μ-Opioid Receptors in Motor Impulsivity

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

Cannabinoid CB1 Receptor Activation Mediates the Opposing Effects of Amphetamine on Impulsive Action and Impulsive Choice

It is well known that acute challenges with psychostimulants such as amphetamine affect impulsive behavior. We here studied the pharmacology underlying the effects of amphetamine in two rat models of impulsivity, the 5-choice serial reaction time task (5-CSRTT) and the delayed reward task (DRT), providing measures of inhibitory control, an aspect of impulsive action, and impulsive choice, respectively. We focused on the role of cannabinoid CB1 receptor activation in amphetamine-induced impulsivity as there is evidence that acute challenges with psychostimulants activate the endogenous cannabinoid system, and CB1 receptor activity modulates impulsivity in both rodents and humans. Results showed that pretreatment with either the CB1 receptor antagonist/inverse agonist SR141716A or the neutral CB1 receptor antagonist O-2050 dose-dependently improved baseline inhibitory control in the 5-CSRTT. Moreover, both compounds similarly attenuated amphetamine-induced inhibitory control deficits, suggesting that CB1 receptor activation by endogenously released cannabinoids mediates this aspect of impulsive action. Direct CB1 receptor activation by Δ9-Tetrahydrocannabinol (Δ9-THC) did, however, not affect inhibitory control. Although neither SR141716A nor O-2050 affected baseline impulsive choice in the DRT, both ligands completely prevented amphetamine-induced reductions in impulsive decision making, indicating that CB1 receptor activity may decrease this form of impulsivity. Indeed, acute Δ9-THC was found to reduce impulsive choice in a CB1 receptor-dependent way. Together, these results indicate an important, though complex role for cannabinoid CB1 receptor activity in the regulation of impulsive action and impulsive choice as well as the opposite effects amphetamine has on both forms of impulsive behavior

The Relationship between Impulsive Choice and Impulsive Action: A Cross-Species Translational Study

Maladaptive impulsivity is a core symptom in various psychiatric disorders. However, there is only limited evidence available on whether different measures of impulsivity represent largely unrelated aspects or a unitary construct. In a cross-species translational study, thirty rats were trained in impulsive choice (delayed reward task) and impulsive action (five-choice serial reaction time task) paradigms. The correlation between those measures was assessed during baseline performance and after pharmacological manipulations with the psychostimulant amphetamine and the norepinephrine reuptake inhibitor atomoxetine. In parallel, to validate the animal data, 101 human subjects performed analogous measures of impulsive choice (delay discounting task, DDT) and impulsive action (immediate and delayed memory task, IMT/DMT). Moreover, all subjects completed the Stop Signal Task (SST, as an additional measure of impulsive action) and filled out the Barratt impulsiveness scale (BIS-11). Correlations between DDT and IMT/DMT were determined and a principal component analysis was performed on all human measures of impulsivity. In both rats and humans measures of impulsive choice and impulsive action did not correlate. In rats the within-subject pharmacological effects of amphetamine and atomoxetine did not correlate between tasks, suggesting distinct underlying neural correlates. Furthermore, in humans, principal component analysis identified three independent factors: (1) self-reported impulsivity (BIS-11); (2) impulsive action (IMT/DMT and SST); (3) impulsive choice (DDT). This is the first study directly comparing aspects of impulsivity using a cross-species translational approach. The present data reveal the non-unitary nature of impulsivity on a behavioral and pharmacological level. Collectively, this warrants a stronger focus on the relative contribution of distinct forms of impulsivity in psychopathology

On meaningful diversity: past, present and future of Wageningen rural sociology

On Meaningful Diversity: Past, present and future of Wageningen rural sociology reflects on 75 years of rural sociology at Wageningen University, the Netherlands. This anniversary book provides a kaleidoscopic overview of the exciting diversity and theoretical depth of the work of the Rural Sociology Group. In addition to introducing key concepts and research approaches, and discussing how these have evolved over time, the book also provides an up-to-date overview of current studies and future agendas. Taken together, the contributions to this book highlight the defining characteristics of the Wageningen rural sociology approach: people’s everyday realities as located in time and space, the investigation of meaningful diversity through empirical and comparative research, and an emphasis on the critical and engaged positioning of the researcher. A timely contribution to the disciplinary literature, this book is a must-read for anyone interested in the history and current issues in rural sociology and the challenges it is taking up in the 21st century

Response contingency directs long-term cocaine-induced neuroplasticity in prefrontal and striatal dopamine terminals

Exposure to addictive substances such as cocaine is well-known to alter brain organisation. Cocaine-induced neuroadaptations depend on several factors, including drug administration paradigm. To date, studies addressing the consequences of cocaine exposure on dopamine transmission have either not been designed to investigate the role of response contingency or focused only on short-term neuroplasticity. We demonstrate a key role of response contingency in directing long-term cocaine-induced neuroplasticity throughout projection areas of the mesocorticolimbic dopamine system. We found enhanced electrically-evoked [3H]dopamine release from superfused brain slices of nucleus accumbens shell and core, dorsal striatum and medial prefrontal cortex three weeks after cessation of cocaine self-administration. In yoked cocaine rats receiving the same amount of cocaine passively, sensitised dopamine terminal reactivity was only observed in the nucleus accumbens core. Control sucrose self-administration experiments demonstrated that the observed neuroadaptations were not the result of instrumental learning per se. Thus, long-term withdrawal from cocaine self-administration is associated with widespread sensitisation of dopamine terminals throughout frontostriatal circuitries

Effects of the CB1 receptor antagonist/inverse agonist SR141716A (SR) on measures of attentional function, compulsivity, and motivation in the 5-CSRTT under conditions of normal or lengthened intertrial interval (ITI).

<p>In total n = 14 animals were included in the analyses and data depict mean±SEM.</p><p>*p<0.05 compared to respective Vehicle control.</p>+<p>p<0.05.</p>++<p>p<0.005 compared to respective ITI = 5 s control.</p

The CB receptor agonist Δ9-Tetrahydrocannabinol does not affect inhibitory control, but reduces impulsive choice.

<p>Effects of acute administration of Δ9-Tetrahydrocannabinol (THC) on the mean (± SEM) number of premature responses made in the 5-CSRTT (a,b) and effects of THC, SR141716A (SR), and their combination on the percentage preference for the larger, delayed reinforcer in the DRT (c,d). ITI: intertrial interval. In total <i>n</i> = 13−14 animals were included in the analyses. Drug doses are expressed as mg/kg. ^*<i>p</i><0.05 and ^**<i>p</i><0.005 versus Vehicle or Vehicle-Vehicle; ^#<i>p</i><0.05 compared to THC-Vehicle, ⁺⁺p<0.005 vs respective ITI 5 s control.</p