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Behavioural sensitization after repeated exposure to Delta 9-tetrahydrocannabinol and cross-sensitization with morphine.
Psychopharmacology (Berl). 2001 Nov; 158(3):259-66.P

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 Delta(9)-tetrahydrocannabinol (Delta(9)-THC) induces behavioural sensitization. In addition we tested the possibility of cross-sensitization between Delta(9)-THC and morphine.

METHODS

Male Sprague-Dawley rats were administered for 3 days, twice daily, with increasing doses of Delta(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 Delta(9)-THC (75 and 150 microg/kg i.v.), with a synthetic cannabinoid agonist WIN55212-2 (75 and 150 microg/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 Delta(9)-THC showed a greater behavioural activation compared to controls in response to challenge with Delta(9)-THC (150 microg/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 (Delta(9)-HC and WIN55212-2, 75 and 150 microg/kg i.v.). The effect of the challenge with Delta(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 Delta(9)-THC induces behavioural sensitization not only to cannabinoids but also to opiates. This cross-sensitization was symmetrical since rats behaviourally sensitized to morphine were also sensitized to cannabinoids. These observations further support the evidence of an interaction between the opioid and the cannabinoid system and might provide a neurobiological basis for a relationship between cannabis use and opiate abuse.

Authors+Show Affiliations

Cadoni C
Department of Toxicology and CNR Center for Neuropharmacology, University of Cagliari, Viale Diaz 182, 09126 Cagliari, Italy.
Pisanu A
No affiliation info available
Solinas M
No affiliation info available
Acquas E
No affiliation info available
Di Chiara G
No affiliation info available

MeSH

Analgesics, Non-NarcoticAnalgesics, OpioidAnimalsDose-Response Relationship, DrugDronabinolDrug Administration ScheduleInjections, IntravenousMaleMorphineRatsRats, Sprague-DawleyStereotyped Behavior

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11713615

Citation

Cadoni, C, et al. "Behavioural Sensitization After Repeated Exposure to Delta 9-tetrahydrocannabinol and Cross-sensitization With Morphine." Psychopharmacology, vol. 158, no. 3, 2001, pp. 259-66.
Cadoni C, Pisanu A, Solinas M, et al. Behavioural sensitization after repeated exposure to Delta 9-tetrahydrocannabinol and cross-sensitization with morphine. Psychopharmacology (Berl). 2001;158(3):259-66.
Cadoni, C., Pisanu, A., Solinas, M., Acquas, E., & Di Chiara, G. (2001). Behavioural sensitization after repeated exposure to Delta 9-tetrahydrocannabinol and cross-sensitization with morphine. Psychopharmacology, 158(3), 259-66.
Cadoni C, et al. Behavioural Sensitization After Repeated Exposure to Delta 9-tetrahydrocannabinol and Cross-sensitization With Morphine. Psychopharmacology (Berl). 2001;158(3):259-66. PubMed PMID: 11713615.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Behavioural sensitization after repeated exposure to Delta 9-tetrahydrocannabinol and cross-sensitization with morphine. AU - Cadoni,C, AU - Pisanu,A, AU - Solinas,M, AU - Acquas,E, AU - Di Chiara,G, PY - 2000/11/07/received PY - 2001/07/04/accepted PY - 2001/11/20/pubmed PY - 2002/2/13/medline PY - 2001/11/20/entrez SP - 259 EP - 66 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 158 IS - 3 N2 - 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 Delta(9)-tetrahydrocannabinol (Delta(9)-THC) induces behavioural sensitization. In addition we tested the possibility of cross-sensitization between Delta(9)-THC and morphine. METHODS: Male Sprague-Dawley rats were administered for 3 days, twice daily, with increasing doses of Delta(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 Delta(9)-THC (75 and 150 microg/kg i.v.), with a synthetic cannabinoid agonist WIN55212-2 (75 and 150 microg/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 Delta(9)-THC showed a greater behavioural activation compared to controls in response to challenge with Delta(9)-THC (150 microg/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 (Delta(9)-HC and WIN55212-2, 75 and 150 microg/kg i.v.). The effect of the challenge with Delta(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 Delta(9)-THC induces behavioural sensitization not only to cannabinoids but also to opiates. This cross-sensitization was symmetrical since rats behaviourally sensitized to morphine were also sensitized to cannabinoids. These observations further support the evidence of an interaction between the opioid and the cannabinoid system and might provide a neurobiological basis for a relationship between cannabis use and opiate abuse. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/11713615/Behavioural_sensitization_after_repeated_exposure_to_Delta_9_tetrahydrocannabinol_and_cross_sensitization_with_morphine_ L2 - https://dx.doi.org/10.1007/s002130100875 DB - PRIME DP - Unbound Medicine ER -