Impact of cannabinoid receptor ligands on behavioural sensitization to antiaggressive methamphetamine effects in the model of mouse agonistic behaviour.
OBJECTIVE
Psychostimulants and cannabinoids can elicit so called behavioural sensitization after repeated administration, a gradually increased behavioural response to a drug. This phenomenon if conditioned by previous pre-treatment with different drug is termed cross-sensitization. The present study was focused on a possible sensitisation to antiaggressive effect of methamphetamine and cross-sensitization to this effect after repeated pre-treatment with cannabinoid CB1 and CB2 receptor ligands with different intrinsic activity (CB1 agonist methanandamide, CB2 agonist JWH 015, and CB1 antagonist AM 251).


METHODS
Behavioural interactions of singly-housed mice with non-aggressive group-housed partners were video-taped and behavioural elements of agonistic behaviour of isolates were recorded in four categories: sociable, timid, aggressive and locomotor.


RESULTS
Repeated administration of methamphetamine elicited a significant sensitization to its antiaggressive effects. Methanandamide pre-treatment provoked cross-sensitization to this methamphetamine effect, whereas pre-treatment with JWH 015 did not. Combined pre-treatment with methamphetamine+AM 251 suppressed the sensitization to antiaggressive effects of methamphetamine.


CONCLUSIONS
Our findings have shown that it is possible to provoke sensitization not only to the stimulatory effects as stated widespread in the literature but also to inhibitory antiaggressive effects of methamphetamine. Furthermore, we confirmed our working hypothesis that it is possible to elicit either cross-sensitization to inhibitory effects of methamphetamine conditioned by repeated pre-treatment with cannabinoid CB1 receptor agonist methanandamide, or suppression of methamphetamine sensitizing influence by co-administration of CB1 receptor antagonist.
Landa
Leos
L
Masaryk University, Faculty of Medicine, Department of Pharmacology, Tomesova 12, 662 43 Brno, Czech Republic. landa@med.muni.cz
Slais
Karel
K
Sulcova
Alexandra
A
D000378:Agonistic Behavior / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D007211:Indoles / Q000494:pharmacology; D008024:Ligands; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D051379:Mice; D008813:Mice, Inbred ICR; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011897:Random Allocation; D043882:Receptors, Cannabinoid / Q000502:physiology*; D018709:Statistics, Nonparametric
D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D000697:Central Nervous System Stimulants; D007211:Indoles; D008024:Ligands; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; C088155:methanandamide; C103505:AM 251; D008694:Methamphetamine; C402944:JHW 015