Differential ontogenesis of three DOI-induced behaviors in mice

Our previous studies have shown that intraperitoneal administration of DOI [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane] simultaneously produces the head-twitch and ear-scratch responses (HTR and ESR, respectively) in mice via activation of 5-HT2A receptors. In the present study, we have investigated the ontogeny of these DOI-induced behaviors in both male and female mice across a wide age range (i.e., postnatal days 7, 14, 18, 22, 28, 35, 42, 63, 120, and 180). We also measured the effects of DOI on the locomotor activity of these mice. In addition to the vehicle, 2 doses of DOI (1 and 2.5 mg/kg) were used in age-matched different male and female groups. The age of onset for significant production of HTR and ESR by both doses of DOI were between postpartum days 14-18 and 18-22, respectively. Maximal HTR frequency to both doses of DOI (66 and 94 HTRs) occurred on postpartum day 28. Thereafter, the HTR frequency tended to decrease with increasing age, but the attenuation did not attain significance. On the other hand, maximal ESR score (37 and 60 ESRs) generally developed between postpartum days 22-35 for the cited doses of DOI. After 35 days of age, the ESR frequency dramatically decreased and, by postnatal day 180, no significant response was obtained to either dose of DOI. Age-matched vehicle-treated male and female control groups exhibited few (1-8) HTRs and ESRs across the age range tested. DOI dose-dependently enhanced locomotor activity in both male and female mice relative to their age- and sex-matched vehicle-treated controls for the first 28 days of life. Thereafter, no significant effect was observed. None of the cited behaviors exhibited gender differences across the age range tested. The present results suggest that DOI-induced changes in HTR, ESR, and locomotor activity develop and mature differentially, but in a similar manner, in male and female mice. Furthermore, unlike DOI-induced HTR, the ability of DOI to produce ear-scratches and to enhance locomotor activity in mice disappears with old age.