Interaction of cannabinoid methanandamide with processes of sensitization to both behavioral and immunological methamphetamine effects in mice.
| Authors | |
|---|---|
| Year of publication | 2004 |
| Type | Article in Proceedings |
| Conference | Abstracts - NIDA International Forum 2004, San Juan, Puerto Rico |
| MU Faculty or unit | |
| Citation | |
| Field | Pharmacology and pharmaceutical chemistry |
| Keywords | methanandamide; methamphetamine; sensitization; mice |
| Description | The phenomenon of sensitization enhancing usually stimulant behavioral response to repeatedly administered drugs of abuse has been described both in laboratory animals and human beings. There is also data available confirming a cross-sensitization between different types of drugs of abuse supporting further the hypothesis that repeated use of one drug of abuse may facilitate the consumption of other drugs. Previously we confirmed the sensitization to methamphetamine (MET) stimulatory effect on locomotor/exploratory behavior, and also to its inhibitory influence on aggression in mice. Furthermore, such sensitization was present in mice cross-sensitized with cannabinoid methanandamide (CAN). Our experiences with behavioral as well as immunological profiles of different cannabinoids received in our collaborative studies with Israel colleagues (Mechoulam R., Fride E.) gave rise to the present study comparing cross-sensitization with CAN to behavioral MET effects with their influences on immune function of leukocytes - phagocytic activity. Not only the behavioral sensitization to MET antiaggressive effects in aggressive singly-housed male mice on paired interactions with non-aggressive group-housed partners but also to inhibitory influence on leukocyte phagocytosis were registered in the present study when challenge doses were given several days apart from the pre-treatment with 5 daily doses of MET. In the same experimental design a cross-sensitization to the antiaggressive efficacy of methamphetamine was found after 5 daily doses of CAN. The 5 day treatment with CAN significantly increased phagocytosis of zymosan by leukocytes in vitro, and did not cross-sensitized to MET 5 challenge doses given 9 days later when the chemiluminometric curve signaling phagocytosis did not vary from the control one. These results confirm an interaction between the endocannabinoid system and MET brain mechanisms, and support further the hypothesis that repeated use of cannabis may smooth the progress of intake of psychostimulant drugs at least. Despite CA is reported as agonist with high affinity at CB1 cannabinoid receptor localized mainly in the CNS it stimulated after repeated doses leukocyte phagocytosis, but did not cross-sensitized to MET suppressive effect on this function. |
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