Abstract |
Early studies in the existing literature suggest that CB2 cannabinoid receptors
(CB2Rs) play a major role in modulating motivation and reward processes. This
Master’s research is focused on understanding CB2Rs’ implication in brain-reward
systems responsible for the expression of reinforcing properties of drugs of abuse,
such as cocaine, and providing further evidence that the endocannabinoid system
could be explored as a potential drug discovery target for the treatment of drug
addiction and reward-dysfunction-related disorders.
The aim of this study was to examine the effects of JWH133, a potent CB2R
agonist, on the systemic cocaine-induced potentiation of brain-stimulation reward
using the intracranial self-stimulation (ICSS) paradigm. Therefore, we ivestigated the
effects of local administration of JWH-133 into the ventral tegmental area (VTA) on
the rewarding efficacy of cocaine. In order to verify the specificity of CB2R’s
implication, reversal of JWH-133 effects was investigated by pre-tratment with the
CB2R antagonist SR144528. Thus, the effects of the different drugs used on the
rewarding efficacy of self-stimulation were inferred using the curve-shift intracranial
self-stimulation paradigm.
Our study indicates that intra-VTA administration of JWH-133 was able to
affect the reward-facilitating effect of cocaine and that these effects were blocked by
pre-administration of SR144528, suggesting CB2R-mediated effects.
These findings support a common conclusion that CB2Rs may constitute new
targets in medication development for treatment of substance abuse and addiction.
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