Abstract
Rationale. Serotonin 5-HT3 receptor antagonists are proposed to serve as potential anti-addictive and anti-psychotic therapies.
Objective. The present study re-examined the hypothesis that the activation of 5-HT3 receptors is required for the development of long-term motor sensitization to repeated cocaine (COC).
Methods. Rats were pretreated with vehicle (VEH) or one of three 5-HT3 receptor antagonists, MDL 72222, Y-25130 or ondansetron, 30 min prior to seven daily COC or saline (SAL) injections. Three weeks later, animals were challenged with COC in a test for sensitization. For comparison, the effects of pretreatment with the dopamine (DA) receptor antagonist fluphenazine and a combination of fluphenazine and Y-25130 were assessed.
Results. Pretreatment with ondansetron, Y-25130, fluphenazine and their combination significantly attenuated COC-induced behaviors during repeated treatment but not on the test for sensitization. MDL 72222 pretreatment enhanced motor sensitization on the test day. In repeated SAL rats, pretreatment with ondansetron, Y-25130 and fluphenazine+Y-25130 enhanced COC-induced rearing on the test for sensitization.
Conclusions. These data indicate the effects of 5-HT3 receptor antagonists on both acute COC-induced motor behavior and COC-induced motor sensitization are compound-selective. As none of the 5-HT3 receptor antagonists attenuated the magnitude of the sensitized motor response to COC in the long term, these data also indicate that like DA receptor activation, 5-HT3 receptor activation is necessary for the full expression of acute COC-induced motor hyperactivity, but it is not required for the development of long-term motor sensitization.
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Szumlinski, K.K., Frys, K.A. & Kalivas, P.W. Pretreatment with serotonin 5-HT3 receptor antagonists produces no observable blockade of long-term motor sensitization to cocaine in rats. Psychopharmacology 165, 329–336 (2003). https://doi.org/10.1007/s00213-002-1274-0
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DOI: https://doi.org/10.1007/s00213-002-1274-0