Effect of the 5-HT3 receptor antagonists, MDL72222 and ondansetron on morphine place conditioning.
The purpose of the present study was to reassess the original findings of Carboni et al. (1988) who suggested that 5-HT3 receptor antagonists may block morphine-induced place conditioning in rats. These workers used a biased protocol with treatments allocated to compartments based on initial preference. In the present study we have adopted an unbiased approach with treatments randomly assigned to conditioning compartment in a counter-balanced fashion. Thus treatments were equally paired between distinct environmental cues. Using this protocol, morphine produced a dose-related place preference (0.3-3 mg/kg SC). Thirty-minute pretreatment with the selective 5-HT3 antagonists, MDL72222 (1 mg/kg SC) and ondansetron (0.01 mg/kg SC) before morphine (1.5 mg/kg SC), significantly antagonized the place conditioning to this treatment. However, with higher doses of ondansetron (0.1-1 mg/kg SC), the antagonism of morphine-induced place preference became variable and dependent on the conditioning compartment. This was probably a reflection of the fact that ondansetron when administered alone also appeared to produce an environmentally dependent place conditioning at these doses. Therefore it is concluded that at certain doses, 5-HT3 receptor antagonists may antagonize morphine place conditioning in a manner consistent with a blockade of the appetitive effects of this drug. However, at higher doses, at least with ondansetron, this antagonism became non-specific and dependent on the training environment. It is suggested that other animal models of opioid reinforcement (e.g., self-administration) are now needed to validate the hypothesis that 5-HT3 receptor antagonists may modify opioid reward.
Higgins
G A
GA
Clinical Psychopharmacology Program, Addiction Research Foundation, Toronto, Ontario, Canada.
Joharchi
N
N
Nguyen
P
P
Sellers
E M
EM
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017294:Ondansetron; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014326:Tropanes / Q000494:pharmacology*
D007093:Imidazoles; D012702:Serotonin Antagonists; D014326:Tropanes; D017294:Ondansetron; D009020:Morphine; C042253:bemesetron