Behavioral and electrophysiological effects of endocannabinoid and dopaminergic systems on salient stimuli

Abstract

Rewarding effects have been related to enhanced dopamine (DA) release in corticolimbic and basal ganglia structures. The DAergic and endocannabinoid interaction in the responses to reward is described. This study investigated the link between endocannabinoid and DAergic transmission in the processes that are related to response to two types of reward, palatable food and novelty. Mice treated with drugs acting on endocannabinoid system (ECS) (URB597, AM251) or DAergic system (haloperidol) were submitted to approach-avoidance conflict tasks with palatable food or novelty. In the same mice, the cannabinoid type-1 (CB1)-mediated GABAergic transmission in medium spiny neurons of the dorsomedial striatum was analyzed. The endocannabinoid potentiation by URB597 magnified approach behavior for reward (food and novelty) and in parallel inhibited dorsostriatal GABAergic neurotransmission. The decreased activity of CB1 receptor by AM251 (alone or with URB597) or of DAergic D2 receptor by haloperidol had inhibitory effects toward the reward and did not permit the inhibition of dorsostriatal GABAergic transmission. When haloperidol was coadministered with URB597, a restoration effect on reward and reward-dependent motor activity was observed, only if the reward was the palatable food. In parallel, the coadministration led to restoring inhibition of CB1-mediated GABAergic transmission. Thus, in the presence of simultaneous ECS activation and inhibition of DAergic system the response to reward appears to be a stimulus-dependent manner.

Pilot clinical observations between food and drug seeking derived from fifty cases attending an eating disorder clinic

“…Psychoactive substances boost DA signaling and sensitize mesolimbic mechanisms that have been developed to modulate the incentive salience of reward processing (Laricchiuta, Musella, Rossi, & Centonze, 2014). Drugs of abuse are willingly self-administered.…”

PYY3–36: Beyond food intake

“…Dopaminergic mechanisms in general, and increased accumbal dopaminergic activity in particular, are critical in regulating the perception and processing of salient stimuli (Berridge and Robinson, 1998;Wise, 2004). For example, manipulations increasing and decreasing dopaminergic activity in the NAc, respectively, enhance and reduce exploratory activity toward novel stimuli (Rebec et al, 1997;Peters et al, 2007;Fukushiro and Frussa--Filho, 2011;Laricchiuta et al, 2014). Furthermore, rats with increased novelty--seeking have a greater behavioral sensitivity to the indirect dopamine receptor agonist cocaine (Beckmann et al, 2011).…”

Individual differences in response to positive and negative stimuli: endocannabinoid-based insight on approach and avoidance behaviors

“…As we recently demonstrated, spontaneous forms of approach and avoidance behaviors rely on ECS modulation in corticolimbic and striatal areas (Laricchiuta et al, 2012b , 2014a , d ).…”

“…To analyze individual differences in spontaneous approach and avoidance behaviors, we tested adolescent (about post-natal day 32nd) C57BL/6JOlaHsd inbred mice in the A/A Y-maze (Laricchiuta et al, 2012b , 2014a , d ). In the large sample of mice (more than seven hundred) tested in the A/A Y-maze task, we assigned the individuals into three phenotypes—avoiding (~6% of individuals that spontaneously reacted with withdrawing responses to the conflicting stimuli), balancing (~25% of individuals that reacted with balanced responses to the conflicting stimuli), and approaching (~7% of individuals that reacted with advancing responses to the conflicting stimuli, Laricchiuta et al, 2012b , 2014d ; Figure 4A ).…”