18-METHOXYCORONARIDINE AND THE HABENULO-INTERPEDUNCULAR PATHWAY: Development of new treatments for opioid addiction

Opioid addiction is a major public health problem and the need for new efficient therapies is immense.18-Methoxycoronaridine (18-MC), an iboga alkaloid congener, has been previously shown to reduce the self-administration of several drugs of abuse, including opioids.18-MC is a potent antagonist of alpha3beta4 nicotinic receptors and this now appears to be the primary mechanism of 18- MC¿s action in the brain. These nicotinic receptors are present in high densities in the nuclei of the habenulo-interpeduncular pathway but not in the mesolimbic pathway, known to be involved in drug addiction.This book describes the modulation of the mesolimbic pathway by the habenulo- interpeduncular pathway during chronic exposure to opioids and examines the role of 18-MC, nicotinic receptors and acetylcholine in such modulation.This book also illustrates the contribution of the latter pathway in 18-MC¿s ability to attenuate opioid withdrawal.The findings described in the book provide evidence that alpha3beta4 nicotinic receptors could be a novel target for anti-addictive therapies.The monograph should be useful to pharmacologists and behavioral neuroscientists.