Behavioral sensitization to delta 9-tetrahydrocannabinol and cross-sensitization with morphine: differential changes in accumbal shell and core dopamine transmission.
Cristina Cadoni, Valentina Valentini, Gaetano Di Chiara
Journal of Neurochemistry August 2008 DOI: 10.1111/j.1471-4159.2008.05503.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Male Sprague-Dawley rats |
| Interventions | Delta(9)-tetrahydrocannabinol (Delta(9)-THC) morphine |
| Dose | Delta(9)-THC 2, 4, and 8 mg/kg i.p. twice daily for 3 days; morphine 10, 20, and 40 mg/kg s.c. twice daily for 3 days; challenge doses: Delta(9)-THC 150 microg/kg i.v., morphine 0.5 mg/kg i.v. |
| Duration | 3-day pretreatment, followed by 14-20 days before microdialysis and challenge the next day |
| Measures | dual probe microdialysis for extracellular dopamine concentrations, behavioral sensitization |
| Topics | Cannabis |
| Key findings | Repeated Delta(9)-THC or morphine treatment produced behavioral sensitization in rats, accompanied by decreased dopamine responses in the nucleus accumbens shell and increased responses in the core after drug challenge. The authors propose that these dopamine changes are similar to those observed in sensitization induced by other drugs of abuse. |
Abstract
Although cannabinoid-induced behavioral sensitization and cross-sensitization with opiates has been recently demonstrated, no information is available on the associated state and responsiveness of dopamine (DA) transmission in the nucleus accumbens (NAc) shell and core. In this study we investigate by means of dual probe microdialysis, the effect of exposure to a sensitizing regimen of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and morphine on the extracellular concentrations of DA under basal conditions and after challenge with Delta(9)-THC and morphine in the NAc shell and core. Different groups of male Sprague-Dawley rats were administered twice daily for 3 days with increasing doses of Delta(9)-THC (2, 4, and 8 mg/kg i.p.), morphine (10, 20, and 40 mg/kg s.c.), and vehicle. After 14-20 days from the last injection, the animals were implanted with two microdialysis probes, one aimed at the NAc shell and the other at the core. The following day animals pre-treated with Delta(9)-THC and vehicle controls were challenged with 150 microg/kg i.v. of Delta(9)-THC or 0.5 mg/kg i.v. of morphine. Animals pre-treated with morphine and their vehicle controls were administered with 150 microg/kg i.v. of Delta(9)-THC. Rats pre-exposed to Delta(9)-THC showed behavioral sensitization associated with a reduced stimulation of DA transmission in the NAc shell and an increased stimulation in the NAc core in response to Delta(9)-THC challenge. Pre-exposure to Delta(9)-THC induced behavioral sensitization to morphine also, but only a reduced stimulation of DA transmission in the NAc shell was observed. Animals pre-treated with morphine showed behavioral sensitization and differential changes of DA in the NAc shell and core in response to Delta(9)-THC challenge with a decreased response in the shell and an increased response in the core. The results show that Delta(9)-THC-induced behavioral sensitization is associated with changes in the responsiveness of DA transmission in the NAc subdivisions that are similar to those observed in the sensitization induced by other drugs of abuse.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 12
- Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study BMJ March 1, 2011
- Cannabis Use and Neuroadaptation: A Call for Δ9-Tetrahydrocannabinol Challenge Studies Frontiers in Psychiatry April 14, 2022
- Cross cultural studies on adolescent cannabis use and psychosis 2011
- Dopamine, γ-aminobutyric acid, and glutamate balance in the nucleus accumbens shell: Differential effects of cannabinoid 1 receptor agonists Δ9-Tetrahydrocannabinol, AM11101, and AM8936. Neuropharmacology June 1, 2026
- Long-term effects of THC exposure on reward learning and motivated behavior in adolescent and adult male rats. Psychopharmacology May 2023
and 7 more in the library
Cites 2
- Adolescent cannabis exposure alters opiate intake and opioid limbic neuronal populations in adult rats. Neuropsychopharmacology March 2007
- Chronic treatment with Delta(9)-tetrahydrocannabinol enhances the locomotor response to amphetamine and heroin. Implications for vulnerability to drug addiction. Neuropharmacology July 1, 2001