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  • Title: Pretreatment with serotonin 5-HT(3) receptor antagonists produces no observable blockade of long-term motor sensitization to cocaine in rats.
    Author: Szumlinski KK, Frys KA, Kalivas PW.
    Journal: Psychopharmacology (Berl); 2003 Feb; 165(4):329-36. PubMed ID: 12451437.
    Abstract:
    RATIONALE: Serotonin 5-HT(3) 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-HT(3) 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-HT(3) 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-HT(3) receptor antagonists on both acute COC-induced motor behavior and COC-induced motor sensitization are compound-selective. As none of the 5-HT(3) 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-HT(3) 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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