This study examines the effect of intravenous self-administration (SA) of either heroin or the cannabinoid receptor agonist WIN 55,212-2 on levels and functionality of mu-opioid (MOR) and CB1-cannabinoid receptors (CB1R) in reward-related brain areas, such as the prefrontal cortex (PFC), nucleus accumbens (NAc), caudate putamen (CP), hippocampus (Hippo), amygdala (Amy), hypothalamus (Hypo) and ventral tegmental area (VTA). [H-3]DAMGO and [H-3]CP-55,940 autoradiography and agonist-stimulated [S-35]GTP gamma S binding were performed on brain sections of rats firmly self-administering heroin or WIN 55,212-2. Animals failing to acquire heroin or cannabinoid SA behaviour as well as drug-naive animals never exposed to experimental apparatus or procedure (home-control group) were used as controls. With respect to control groups, which displayed very similar values, rats SA heroin showed increased MOR binding in the NAc (+174%), CP (+165%), Hippo (+121%), VTA (+175%), an enhanced CB1R density localized in the Amy (+147%) and VTA (+37%), and a widespread increased CB1 receptor functionality in the PFC (+95%), NAc (+313%), CP (+265%), Hippo (+38%), Amy (+221%). In turn, cannabinoid SA differently modulates CB1R binding in the Amy (+47%), Hypo (+94%), Hippo (-23%), VTA (-15%), and increases MOR levels (PFC: +124%; NAc: +68%; CP: +80%; Hippo: +73%; Amy: +99%) and efficiency (Hippo: +518%; Amy: +173%; Hypo: +188%). These findings suggest that voluntary chronic intake of opioids or cannabinoids induces reciprocal but differential regulation of MORs and CB1Rs density and activity in brain structures underlying drug-taking and drug-seeking behaviour, which could represent long-term neuroadaptations contributing to the development of drug addiction and dependence.

Bidirectional regulation of mu-opioid and CB1-cannabinoid receptor in rats self-administering heroin or WIN 55,212-2

VIGANO', DANIELA GIULIA;RUBINO, TIZIANA;PAROLARO, DANIELA
2007

Abstract

This study examines the effect of intravenous self-administration (SA) of either heroin or the cannabinoid receptor agonist WIN 55,212-2 on levels and functionality of mu-opioid (MOR) and CB1-cannabinoid receptors (CB1R) in reward-related brain areas, such as the prefrontal cortex (PFC), nucleus accumbens (NAc), caudate putamen (CP), hippocampus (Hippo), amygdala (Amy), hypothalamus (Hypo) and ventral tegmental area (VTA). [H-3]DAMGO and [H-3]CP-55,940 autoradiography and agonist-stimulated [S-35]GTP gamma S binding were performed on brain sections of rats firmly self-administering heroin or WIN 55,212-2. Animals failing to acquire heroin or cannabinoid SA behaviour as well as drug-naive animals never exposed to experimental apparatus or procedure (home-control group) were used as controls. With respect to control groups, which displayed very similar values, rats SA heroin showed increased MOR binding in the NAc (+174%), CP (+165%), Hippo (+121%), VTA (+175%), an enhanced CB1R density localized in the Amy (+147%) and VTA (+37%), and a widespread increased CB1 receptor functionality in the PFC (+95%), NAc (+313%), CP (+265%), Hippo (+38%), Amy (+221%). In turn, cannabinoid SA differently modulates CB1R binding in the Amy (+47%), Hypo (+94%), Hippo (-23%), VTA (-15%), and increases MOR levels (PFC: +124%; NAc: +68%; CP: +80%; Hippo: +73%; Amy: +99%) and efficiency (Hippo: +518%; Amy: +173%; Hypo: +188%). These findings suggest that voluntary chronic intake of opioids or cannabinoids induces reciprocal but differential regulation of MORs and CB1Rs density and activity in brain structures underlying drug-taking and drug-seeking behaviour, which could represent long-term neuroadaptations contributing to the development of drug addiction and dependence.
Addiction; Autoradiography; Binding; Reward; Self-administration;
Fattore, L; Vigano', DANIELA GIULIA; Fadda, P; Rubino, Tiziana; Fratta, W; Parolaro, Daniela
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11383/12631
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