title: The anabolic steroid nandrolone alters cannabinoid self-administration and brain CB1receptor density and function.
abstract: Clinical and pre-clinical observations indicate that anabolic-androgenic steroids can induce neurobiological changes that alter the rewarding effects of drugs of abuse. In this study, we investigated the effect of the anabolic steroid nandrolone on the rewarding properties of the cannabinoid CB1receptor agonist WIN55,212-2 (WIN) in rats. Lister Hooded male rats were treated intramuscularly with nandrolone (15mg/kg) or vehicle for 14 consecutive days, and then allowed to self-administer WIN (12.5μg/kg/infusion) intravenously. After reaching stable drug intake, self-administration behavior was extinguished to examine drug- and cue-induced reinstatement of cannabinoid-seeking behavior. Other behavioral parameters presumed to influence drug-taking and drug-seeking behaviors were examined to gain more insight into the behavioral specificity of nandrolone treatment. Finally, animals were sacrificed for analysis of CB1receptor density and function in selected brain areas. We found that nandrolone-treated rats self-administered up to 2 times more cannabinoid than vehicle-treated rats, but behaved similarly to control rats when tested for drug- and cue-induced reinstatement of cannabinoid-seeking behavior. Enhanced cannabinoid intake by nandrolone-treated rats was not accompanied by changes in locomotor activity, sensorimotor gating, or memory function. However, our molecular data show that after chronic WIN self-administration nandrolone-treated rats display altered CB1receptor density and function in selected brain areas. We hypothesize that increased cannabinoid self-administration in nandrolone-treated rats results from a nandrolone-induced decrease in reward function, which rats seem to compensate by voluntarily increasing their cannabinoid intake. Altogether, our findings corroborate the hypothesis that chronic exposure to anabolic-androgenic steroids induces dysfunction of the reward pathway in rats and might represent a potential risk factor for abuse of cannabis and other drugs in humans.
authors.affiliation: Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen 9713ZG, the Netherlands.
authors.forename: Dicky
authors.initials: D
authors.lastname: Struik
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, SS 554Km 4,500, 09042 Monserrato, CA, Italy; Centre of Excellence "Neurobiology of Dependence", University of Cagliari, Cittadella Universitaria di Monserrato, SS 554 Km 4,500, 09042 Monserrato, CA, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Fadda
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, SS 554Km 4,500, 09042 Monserrato, CA, Italy.
authors.forename: Tamara
authors.initials: T
authors.lastname: Zara
authors.affiliation: Department of Biotechnology and Life Sciences, and Neuroscience Center University of Insubria, Busto Arsizio, VA, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Zamberletti
authors.affiliation: Department of Biotechnology and Life Sciences, and Neuroscience Center University of Insubria, Busto Arsizio, VA, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Rubino
authors.affiliation: Department of Biotechnology and Life Sciences, and Neuroscience Center University of Insubria, Busto Arsizio, VA, Italy; Zardi Gori Foundation, Via Curtatone 25, Milano, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Parolaro
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, SS 554Km 4,500, 09042 Monserrato, CA, Italy; Centre of Excellence "Neurobiology of Dependence", University of Cagliari, Cittadella Universitaria di Monserrato, SS 554 Km 4,500, 09042 Monserrato, CA, Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Fratta
authors.affiliation: Centre of Excellence "Neurobiology of Dependence", University of Cagliari, Cittadella Universitaria di Monserrato, SS 554 Km 4,500, 09042 Monserrato, CA, Italy; CNR Institute of Neuroscience-Cagliari, National Research Council, Italy. Electronic address: lfattore@in.cnr.it.
authors.forename: Liana
authors.initials: L
authors.lastname: Fattore
mesh_terms: D045930:Anabolic Agents / Q000008:administration & dosage*; D000818:Animals; D001921:Brain / Q000187:drug effects*; D002186:Cannabinoids / Q000008:administration & dosage*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D009277:Nandrolone / Q000008:administration & dosage*; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D012201:Reward; D012646:Self Administration / Q000379:methods; D055139:Sensory Gating / Q000187:drug effects; D013256:Steroids / Q000008:administration & dosage*
chemical_list: D045930:Anabolic Agents; D002186:Cannabinoids; D043884:Receptor, Cannabinoid, CB1; D013256:Steroids; D009277:Nandrolone
keywords: Anabolic steroid; Cannabinoid CB(1) receptors; Co-abuse; Drug addiction; Nandrolone; Nandrolone decanoate (Pubchem CID 9677); Reward; WIN55,212-2 (PubChem CID 6604176)