Sensitization to cocaine is inhibited after intra-accumbal GR103691 or rimonabant, but it is enhanced after co-infusion indicating functional interaction between accumbens D3 and CB1 receptors

Abstract

Dopamine D(3) receptors within the nucleus accumbens are critical for the development and consolidation of sensitization, and cannabinoid CB(1) receptors are critical for the expression of sensitization. Co-blockade of D(3) and CB(1) receptors exert opposite effects to blockade of these receptors separately, revealing the existence of a functional interaction between them.

Cannabinoid CB1 receptors mediate the effects of corticotropin‐releasing factor on the reinstatement of cocaine seeking and expression of cocaine‐induced behavioural sensitization

“…These results parallel the inhibitory effects of AM251 we have shown on CRF‐induced reinstatement in the present report and on CRF‐induced anxiety in another recent study (Kupferschmidt et al ., 2011c). They are also consistent with other reports demonstrating a mediating role for CB 1 (Filip et al ., 2006; Ramiro‐Fuentes and Fernandez‐Espejo, 2011) and CRF receptors (Przegaliński et al ., 2005; Erb and Brown, 2006) in cocaine‐induced expression of behavioural sensitization. Taken together, this evidence suggests that CB 1 receptors may mediate the expression of cocaine‐induced locomotor sensitization through a CRF‐dependent mechanism.…”

“…Two regions of interest in the effects of AM251 on CRF‐ and cocaine‐induced expression of sensitization are the NAc and VTA. The role of both nuclei in behavioural sensitization is well established (Steketee and Kalivas, 2011), and there is recent evidence that intra‐NAc administration of the CB 1 receptor antagonist, SR141716A, blocks the expression of cocaine‐induced sensitization (Ramiro‐Fuentes and Fernandez‐Espejo, 2011). With respect to the VTA, repeated exposures to cocaine are known to sensitize VTA dopamine neurons to the activational effects of both cocaine and CRF (Bonci and Williams, 1996; Kalivas and Duffy, 1998; Hahn et al ., 2009).…”

“…Our research program for studies on psychostimulant sensitization has developed using the Wistar rats, in part because this albino strain offers a suitable contrast of a white object on a black apparatus background, which is ideal for the purposes of configuring our activity monitoring system (Ethovision by Noldus, Wageningen, the Netherlands). In addition, this strain has been used widely in studies of psychostimulant sensitization (Erb et al ., 2003; Przegaliński et al ., 2005; Ramiro‐Fuentes and Fernandez‐Espejo, 2011).…”

“…Somewhat in contrast, pretreatment with the selective CB 1 receptor antagonist, AM251, was without effect on cocaine‐induced reinstatement of an extinguished cocaine conditioned place preference (CPP) but blocked its reinstatement by forced‐swim stress (Vaughn et al ., 2011). Although the role of CB 1 receptors in cocaine‐induced behavioural sensitization has been the subject of fewer investigations, studies carried out to date indicate an antagonizing effect of acute SR141716A administration on the expression of cocaine‐induced locomotor sensitization to a cocaine challenge (Filip et al ., 2006; Ramiro‐Fuentes and Fernandez‐Espejo, 2011).…”

Cannabinoid CB1 and Dopamine D1 Receptors Partnership in the Modulation of Emotional Neural Processing

“…Yet, less is known about the functional interaction between cannabinoid and dopaminergic receptors in the control of emotional behavior. Much of our understanding has been improved only recently by studies using knockout (KO) animals (Micale et al, 2009; Ortega-Alvaro et al, 2011; Thanos et al, 2011), behavioral approaches (Ramiro-Fuentes and Fernandez-Espejo, 2011; Zarrindast et al, 2011), or neuroanatomical and electrophysiological techniques (Chiu et al, 2010). …”