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 depende ntly reduces the 5-HT2-receptor-mediated DOI ,5-dimethoxy-4-iodophenyl )-2-aminopropane]-induced head-twitch response (HTR) in mice via indir ect stimulation of the inhibitory adrenergic alpha(2)- and serotonergi c 5-HT1A receptors. In addition, the inhibitory capacity of cocaine wa s enhanced fourfold in mice with 5-HT2-receptor supersensitivity induc ed 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-induce d HTR. Two reserpine injections did not further enhance this supersens itivity effect. Once reserpinized 5-HT2-receptor supersensitive animal s were less responsive to the inhibitory effects of cocaine on the DOI -induced behavior than were the mice, as reported previously, that wer e 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 to gether with previously published data, the present investigation lends further support for the importance of endogenous levels of 5-HT and n orepinephrine on the ability of cocaine to attenuate the DOI-induced H TR.