The effects of acute cocaine administration on the DOI-induced head-twitch response in reserpinized mice

Previously it was shown that acute cocaine administration dose dependently reduces the 5-HT2-receptor-mediated DOI [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane]-induced head-twitch response (HTR) in mice via indirect stimulation of the inhibitory adrenergic alpha 2- and serotonergic 5-HT1A receptors. In addition, the inhibitory capacity of cocaine was enhanced fourfold in mice with 5-HT2-receptor supersensitivity induced by a single injection of DOI 48 h prior to experimentation. The aim of the present investigation was to determine the inhibitory capacity of cocaine in reserpinized mice. A single injection of reserpine 48 h prior to DOI administration caused supersensitivity in the DOI-induced HTR. Two reserpine injections did not further enhance this supersensitivity effect. Once reserpinized 5-HT2-receptor supersensitive animals were less responsive to the inhibitory effects of cocaine on the DOI-induced behavior than were the mice, as reported previously, that were made supersensitive by DOI pretreatment. The inhibitory capacity of cocaine was further attenuated when mice were reserpinized twice prior to determination of its effects on the DOI-induced behavior. Taken together with previously published data, the present investigation lends further support for the importance of endogenous levels of 5-HT and norepinephrine on the ability of cocaine to attenuate the DOI-induced HTR.