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- Title
Behavioural sensitization after repeated exposure to Δ[sup 9] -tetrahydrocannabinol and cross-sensitization with morphine.
- Authors
Cadoni, Cristina; Pisanu, Augusta; Solinas, Marcello; Acquas, Elio; Chiara, Gaetano
- Abstract
Rationale: Repeated exposure to several drugs of abuse has been reported to induce behavioural sensitization. So far no evidence has been provided that such a phenomenon also applies to cannabinoids. Objectives: In this study we investigated if repeated exposure to Δ[sup 9] -tetrahydrocannabinol (Δ[sup 9] -THC) induces behavioural sensitization. In addition we tested the possibility of cross-sensitization between Δ[sup 9] -THC and morphine. Methods: Male Sprague-Dawley rats were administered for 3 days, twice daily, with increasing doses of Δ[sup 9] -tetrahydrocannabinol (2, 4 and 8 mg/kg i.p.) or increasing doses of morphine (10, 20 and 40 mg/kg s.c.) or vehicle. After a washout of 14 days the animals were challenged with Δ[sup 9] -THC (75 and 150 µg/kg i.v.), with a synthetic cannabinoid agonist WIN55212–2 (75 and 150 µg/kg i.v.) or with morphine (0.5 mg/kg i.v.), through a catheter inserted into the left femoral vein 24 h before, and the behaviour recorded. Results: Rats previously administered with Δ[sup 9] -THC showed a greater behavioural activation compared to controls in response to challenge with Δ[sup 9] -THC (150 µg/kg i.v.) and to challenge with morphine (0.5 mg/kg i.v.). Similar to that observed after repeated opiates, this behavioural sensitization was characterized by stereotyped activity. Animals administered with a schedule of morphine that induces behavioural sensitization to morphine also showed a behavioural sensitization to challenge with cannabinoids (Δ[sup 9] -THC and WIN55212–2, 75 and 150 µg/kg i.v.). The effect of the challenge with Δ[sup 9] -THC was prevented by the administration of the CB1 antagonist SR141716A (1 mg/kg i.p.), 40 min beforehand. Conclusions: The results of the present study demonstrate that repeated exposure to Δ[sup 9] -THC induces behavioural sensitization not only to cannabinoids but also to opiates. This cross-sensitization w...
- Subjects
TETRAHYDROCANNABINOL; ANXIETY sensitivity; MORPHINE; PHYSIOLOGY; DRUG side effects
- Publication
Psychopharmacology, 2001, Vol 158, Issue 3, p259
- ISSN
0033-3158
- Publication type
Article
- DOI
10.1007/s002130100875