Adolescent exposure to chronic delta-9-tetrahydrocannabinol blocks opiate dependence in maternally deprived rats.
Lydie J Morel, Bruno Giros, Valérie Daugé
Neuropsychopharmacology October 2009 DOI: 10.1038/npp.2009.70 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled experimental animal study Peer reviewed |
|---|---|
| Population | Maternally deprived and non-deprived (animal facility rearing) rats |
| Interventions | Dronabinol (natural delta-9 tetrahydrocannabinol THC) Morphine |
| Duration | Chronic exposure during postnatal days 35-49, with 2 weeks of washout before testing |
| Measures | place preference test, oral self-administration test, preproenkephalin (PPE) mRNA levels, CB1 receptor density and functionality, mu-opioid receptor density and functionality |
| Topics | Addiction Cannabis |
| Key findings | The authors report that chronic adolescent dronabinol exposure increased morphine reward sensitivity and reduced striatal preproenkephalin mRNA in non-deprived rats, while in maternally deprived rats it normalized preproenkephalin levels and morphine consumption and suppressed morphine conditioning. They argue these findings point to self-medication use of cannabis in individuals exposed to adverse postnatal environments. |
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 mu-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 mu-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.
Comparable studies
Other preclinical and animal studies on cannabis for addiction, most cited first.
Citations in the library
Cites 7
- Modulation of excitatory synaptic transmission by Delta 9-tetrahydrocannabinol switches from agonist to antagonist depending on firing rate. Molecular Pharmacology April 2009
- The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. British Journal of Pharmacology January 2008
- Adolescent cannabis exposure alters opiate intake and opioid limbic neuronal populations in adult rats. Neuropsychopharmacology March 2007
- Functional tolerance and blockade of long-term depression at synapses in the nucleus accumbens after chronic cannabinoid exposure. Journal of Neuroscience June 15, 2003
- Regulation of cannabinoid CB1 receptors in the central nervous system by chronic cannabinoids. Critical reviews in neurobiology 2003
and 2 more in the library