Compromised dopaminergic neurotransmission results in a wide variety of pathophysiological states such as schizophrenia, Parkinson’s disease and drug addiction. The endogenous cannabinoid system has been clearly implicated in each of these debilitating conditions, but a link between maladaptive dopamine ...
Compromised dopaminergic neurotransmission results in a wide variety of pathophysiological states such as schizophrenia, Parkinson’s disease and drug addiction. The endogenous cannabinoid system has been clearly implicated in each of these debilitating conditions, but a link between maladaptive dopamine dynamics and signaling at cannabinoid receptors is still unclear. It is therefore of paramount importance to examine maladaptive dopamine activity and to what extent this involves changes in the way endogenous cannabinoid tone modulates dopamine dynamics under normal and pathological conditions. The topic will start by a sophisticated anatomical study of time-dependent alterations of CB1 receptor expression during development, specifically in corticostriatal circuits (Van Waes, Siman, Tseng and Steiner). This will then be followed by an exploration of the role of new players (i.e., adenosine) in the tight relationship between endocannabinoid signaling and D2 receptor activation in the production of long-term synaptic plasticity in the dorsal striatum (Mathur and Lovinger). Next, we will examine reward processing in the ventral striatum in a review, which will highlight how dopaminergic neurons in the VTA can regulate their afferent input via activation of CB1 receptors following the generation of endocannabinoids (2AG principally). The authors postulate that such exquisite modulation is critical in the production of normal motivated behaviors (Melis, Muntoni and Pistis). This hypothesis is explored in a behavioral setting in report showing that activation of CB1 receptors potentiates the hedonic effects of a highly palatable tastant, through a potentiation of dopamine release in the nucleus accumbens. Importantly it is shown that CB1 receptor stimulation is devoid of effects when an aversive tastant is utilized suggesting a primary role of CB1 receptor activation on dopaminergic information processing directed towards the detection and valuation of rewards (De Luca, Solinas, Bimpisidis, Goldberg and Di Chiara).
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