Title:Individual Differences and Vulnerability to Drug Addiction: A Focus on the Endocannabinoid System
Volume: 14
Issue: 4
Author(s): Claudia Sagheddu and Miriam Melis
Affiliation:
Keywords:
Dopamine, drug addiction, endocannabinoid, lipids, midbrain, vulnerability.
Abstract: Vulnerability to drug addiction depends upon the interactions between the biological makeup
of the individual, the environment, and age. These interactions are complex and difficult to tease
apart. Since dopamine is involved in the rewarding effects of drugs of abuse, it is postulated that innate
differences in mesocorticolimbic pathway can influence the response to drug exposure. In particular,
higher and lower expression of dopamine D2 receptors in the ventral striatum (i.e. a marker of
dopamine function) has been considered a putative protective and a risk factor, respectively, that can
influence one's susceptibility to continued drug abuse as well as the transition to addiction. This
phenomenon, which is phylogenetically preserved, appears to be a compensatory change to increased impulse activity of
midbrain dopamine neurons. Hence, dopamine neuronal excitability plays a fundamental role in the diverse stages of the
drug addiction cycle. In this review, a framework for the evidence that modulation of dopamine neuronal activity plays in
the context of vulnerability to drug addiction will be presented. Furthermore, since endogenous cannabinoids serve as
retrograde messengers to shape afferent neuronal activity in a short- and long-lasting fashion, their role in individual
differences and vulnerability to drug addiction will be discussed.
