Repeated cocaine administration does not affect 5-HT receptor subtypes (5-HT_1A, 5-HT₂) in several rat brain regions

In order to examine whether cocaine-induced behavioral sensitization is modulated by changes in serotonin receptor subtypes, we measured the binding of [³H]8-hydroxy-2-(di-n-propylamino)tetralin (³H]8-OH-DPAT) to 5-HT_1A receptors and of [³H]-ketanserin to 5-HT₂ receptors in various brain regions of cocaine-treated and saline-treated (control) rats. As previously reported, repeated administration of cocaine resulted in behavioral sensitization. Stereotypic scores with the cocaine challenge were significantly (P < 0.05) higher in cocaine-pretreated animals than in the saline-pretreated group. Neither acute nor chronic cocaine administration significantly altered the number (B_max) or the affinity (K_D) of either [³H]8-OH-DPAT or [³H]ketanserin binding sites in any of the brain regions examined. These results suggest that the enhanced functional sensitivity of 5-HT_1A or 5-HT₂ receptor subtypes seen with cocaine may be associated with alterations in processes distal to receptors rather than changes in the number or the affinity of the receptors.