Anatomic and physiologic reference values in least shrews (Cryptotis parva).

BACKGROUND AND PURPOSE: The least shrew is an established animal model for reproductive and pharmacologic research. Biologic reference data are needed to assess animal health status and provide a rationale for use of novel statistical programs to evaluate the effects of orally administered substances in toxicologic and pharmacologic studies. METHODS: Organ weights, blood biochemical and hematologic values, and food and water consumption data were collected from 50-day-old shrews after two weeks' consumption of a standard feline diet. RESULTS: In general, data correlated well with values reported for other mammalian species. Plasma phosphorus concentration was high. There was a significant difference in food and water consumption per gram of body weight between shrews at lower and upper (+/- 1 SD) weight ranges for the study. The 3.2-g animals consumed 27% more food per gram of body weight than did the 5.0-g animals. CONCLUSIONS: The high phosphorus concentration was attributed to hemolysis resulting from the axillary cut method of blood sample collection. The small size of the shrew allowed demonstration of the Kleiber effect within a +/- 1 SD weight range in a single species. The phenomenon necessitates the use of statistical methods other than the typical tests establishing the significance of the differences between the means of groups for oral toxicologic and pharmacologic studies.

Prolonged deficits in presynaptic serotonin function following withdrawal from chronic cocaine exposure as revealed by 5-HTP-induced head-twitch response in mice.

Recent in vivo microdialysis studies have indicated that presynaptic deficits occur in brain 5-HT neurochemistry during cocaine withdrawal. The purpose of the present study was to utilize the head-twitch response (HTR) produced by 5-hydroxytryptophan (5-HTP) to investigate the dose- and time-response effects of this deficit. The HTR is considered to be a sensitive model for activation of central postsynaptic 5-HT2A receptors in rodents. Thus, different groups of mice were injected with cocaine twice daily (0, 0.1, 0.5, 2.5, 5 or 10 mg/kg, i.p.) for 7 or 13 days. During HTR testing, at 24 h following last injection, the treated mice received either 1) no cocaine; 2) their corresponding daily dose as challenge injection; or 3) a 10 mg/kg challenge dose. In a second series of experiments, extended abstinence studies were performed under the conditions of experimental protocols 1 and 2 for both 7- and 13-day cocaine (0, 0.5 and 5 mg/kg, twice daily) exposure regimens at 24, 48, 72 and 96 h following last cocaine injection. In protocol 3, the effects of a 10 mg/kg challenge dose of cocaine were studied following prolonged withdrawal from chronic cocaine exposure (0, 0.5, 5 and 10 mg/kg, twice daily for 7 and 13 days) at 24, 96 and 240 h abstinence. In experimental protocol 1 at 24 h abstinence in the 7 day exposure group, only lower doses of cocaine (0.5-2.5 mg/kg) significantly attenuated the 5-HTP-induced HTR. The deficit in 0.5 mg/kg group persisted up to 72 h abstinence. Although in the 13 day cocaine exposure groups (experimental paradigm 1) mean HTRs were generally reduced, they however failed to attain statistical significance throughout the 96 h abstinence. In protocol 2 very low challenge doses of cocaine (0.1-0.5 mg/kg) in their corresponding pretreatment groups significantly reduced the behavior at diverse abstinence intervals in both 7- and 13-day exposure regimens relative to their chronically vehicle-treated controls which had received a vehicle challenge injection during HTR testing. Unlike small doses of cocaine, larger challenge doses (5-10 mg/kg) of the stimulant potentiated the HTR score at various abstinence periods. However, the degree of the potentiations are considerably less than the ability of acute cocaine administration in enhancing the 5-HTP-induced HTR. The 10 mg/kg challenge injection in experimental protocol 3 at 24 h abstinence in the 7-day exposed mice attenuated the 5-HTP-induced HTR in 0.5, 5 and 10 mg/kg cocaine-treated groups relative to their chronic vehicle-treated controls receiving a 10 mg/kg challenge cocaine injection. The deficit in chronic 10 mg/kg cocaine-exposed mice persisted up to 240 h postcocaine abstinence. On the other hand, in the 13-day regimen, the challenge 10 mg/kg dose exhibited significant potentiations at 24 h and at 96 h for 5 and 0.5 mg/kg chronic cocaine doses respectively, but it also produced significant deficits in 0.5 and 10 mg/kg chronic doses of cocaine at 240 h abstinence. Overall, the present results suggest that enduring deficits occur in presynaptic serotonin neurochemistry and serotonergic adaptive mechanisms are exquisitely sensitive to chronic administration of low- and high-doses of cocaine.

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.