Adicción y sistema cannabinoide endógeno: papel del receptor para cannabinoides CB1 en la fisiología de las neuronas dopaminérgicas mesotelencefálicas

Abstract

The endogenous cannabinoid transmission is a new cell signalling system constituted by the cannabi- noid CB-1 and CB2 receptors, as well as by several lipid transmitters including anandamide and 2-arachi- donoylglycerol.The cannabinoid receptors are the pharmacological targets of the psychoactive consti- tuents of used as illegal recreational drugs. Several lines of research using animal models have established that cannabis sativ a preparations, commonly cannabinoids are drugs that modify the activity of the brain reward system, specially the physiology of mesotelencephalic dopaminergic neurones, in a way that resemble the actions of ethanol or the opiates. The present work analyse the anatomical, biochemi- cal and pharmacological evidences that support the role of the endogenous cannabinoid system as a modulator of dopamine transmission in the brain. Cannabinoid CB-1 receptor are present in both, dopa- mine receptor-containing neurones and mesencepha- lic and hypothalamic dopaminergic neurones. Moreo- ver, the pharmacological stimulation of striatal dopamine D-2 receptors is the most potent activator of anandamide release known to date. The released anandamide will act as an endogenous break to the hyperactivity associated with a high dopaminergic output. These findings allow us to propose that drugs which interfere with the endogenous cannabinoid system might be useful as a therapy in that problems where the dopamine system intervene as addictions