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Adolescent Exposure to Chronic Delta-9-Tetrahydrocannabinol Blocks Opiate Dependence in Maternally Deprived Rats
Lydie J Morel1,2,3,5, Bruno Giros1,2,3,4 and Valérie Daugé1,2,3
1Institut National de la Santé et de la Recherche Médicale (INSERM), U952, Université Pierre et Marie Curie, 9 quai Saint Bernard, Paris, Ile de France, France
2Centre National de la Recherche Scientifique (CNRS), UMR 7224, Université Pierre et Marie Curie, 9 quai Saint Bernard, Paris, Ile de France, France
3UMPC Université Paris 06, 9 quai Saint Bernard, Paris, Ile de France, France
4Department of Psychiatry, Douglas Hospital Research Center, McGill University, boulevard Lasalle, Verdun, QC, Canada
5Université Paris Descartes, 12 rue de l'Ecole de médecine, Paris, Ile de France, France
Correspondence: Dr V Daugé, Physiopathologie des maladies du système nerveux central, INSERM UMRs 952, Université Pierre et Marie Curie, 9 quai St-Bernard, Paris, ile de france, 75005, France, Tel: 331 44 27 61 09, E-mail: valerie.dauge@snv.jussieu.fr
Received 16 April 2009; Revised 19 May 2009; Accepted 21 May 2009; Published online 24 June 2009.
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Abstract
Maternal deprivation in rats specifically leads to a vulnerability to opiate dependence. However, the impact of cannabis exposure during adolescence on this opiate vulnerability has not been investigated. Chronic dronabinol (natural delta-9 tetrahydrocannabinol, THC) exposure during postnatal days 35—49 was made in maternal deprived (D) or non-deprived (animal facility rearing, AFR) rats. The effects of dronabinol exposure were studied after 2 weeks of washout on the rewarding effects of morphine measured in the place preference and oral self-administration tests. The preproenkephalin (PPE) mRNA levels and the relative density and functionality of CB1, and μ-opioid receptors were quantified in the striatum and the mesencephalon. Chronic dronabinol exposure in AFR rats induced an increase in sensitivity to morphine conditioning in the place preference paradigm together with a decrease of PPE mRNA levels in the nucleus accumbens and the caudate—putamen nucleus, without any modification for preference to oral morphine consumption. In contrast, dronabinol treatment on D-rats normalized PPE decrease in the striatum, morphine consumption, and suppressed sensitivity to morphine conditioning. CB1 and μ-opioid receptor density and functionality were not changed in the striatum and mesencephalon of all groups of rats. These results indicate THC potency to act as a homeostatic modifier that would worsen the reward effects of morphine on naive animals, but ameliorate the deficits in maternally D-rats. These findings point to the self-medication use of cannabis in subgroups of individuals subjected to adverse postnatal environment.
Keywords:
maternal deprivation, adolescent chronic delta-9-tetrahydrocannabinol, morphine place preference, oral morphine self-administration, preproenkephalin mRNA, CB1 μ-opioid receptors
Source: Adolescent Exposure to Chronic Delta-9-Tetrahydrocannabinol Blocks Opiate Dependence in Maternally Deprived Rats
Lydie J Morel1,2,3,5, Bruno Giros1,2,3,4 and Valérie Daugé1,2,3
1Institut National de la Santé et de la Recherche Médicale (INSERM), U952, Université Pierre et Marie Curie, 9 quai Saint Bernard, Paris, Ile de France, France
2Centre National de la Recherche Scientifique (CNRS), UMR 7224, Université Pierre et Marie Curie, 9 quai Saint Bernard, Paris, Ile de France, France
3UMPC Université Paris 06, 9 quai Saint Bernard, Paris, Ile de France, France
4Department of Psychiatry, Douglas Hospital Research Center, McGill University, boulevard Lasalle, Verdun, QC, Canada
5Université Paris Descartes, 12 rue de l'Ecole de médecine, Paris, Ile de France, France
Correspondence: Dr V Daugé, Physiopathologie des maladies du système nerveux central, INSERM UMRs 952, Université Pierre et Marie Curie, 9 quai St-Bernard, Paris, ile de france, 75005, France, Tel: 331 44 27 61 09, E-mail: valerie.dauge@snv.jussieu.fr
Received 16 April 2009; Revised 19 May 2009; Accepted 21 May 2009; Published online 24 June 2009.
Top of page
Abstract
Maternal deprivation in rats specifically leads to a vulnerability to opiate dependence. However, the impact of cannabis exposure during adolescence on this opiate vulnerability has not been investigated. Chronic dronabinol (natural delta-9 tetrahydrocannabinol, THC) exposure during postnatal days 35—49 was made in maternal deprived (D) or non-deprived (animal facility rearing, AFR) rats. The effects of dronabinol exposure were studied after 2 weeks of washout on the rewarding effects of morphine measured in the place preference and oral self-administration tests. The preproenkephalin (PPE) mRNA levels and the relative density and functionality of CB1, and μ-opioid receptors were quantified in the striatum and the mesencephalon. Chronic dronabinol exposure in AFR rats induced an increase in sensitivity to morphine conditioning in the place preference paradigm together with a decrease of PPE mRNA levels in the nucleus accumbens and the caudate—putamen nucleus, without any modification for preference to oral morphine consumption. In contrast, dronabinol treatment on D-rats normalized PPE decrease in the striatum, morphine consumption, and suppressed sensitivity to morphine conditioning. CB1 and μ-opioid receptor density and functionality were not changed in the striatum and mesencephalon of all groups of rats. These results indicate THC potency to act as a homeostatic modifier that would worsen the reward effects of morphine on naive animals, but ameliorate the deficits in maternally D-rats. These findings point to the self-medication use of cannabis in subgroups of individuals subjected to adverse postnatal environment.
Keywords:
maternal deprivation, adolescent chronic delta-9-tetrahydrocannabinol, morphine place preference, oral morphine self-administration, preproenkephalin mRNA, CB1 μ-opioid receptors
Source: Adolescent Exposure to Chronic Delta-9-Tetrahydrocannabinol Blocks Opiate Dependence in Maternally Deprived Rats
