Effects of Ceruletide, Administered Singly and in Combination with Central-Acting Drugs, on Discrete Shuttle Avoidance Response in Mice

Abstract

Abstract-The single administration of ceruletide at 10-300 '"g/kg, i.p., slightly but significantly decreased the response rate (frequency of shuttles) under a discrete avoidance task in mice. Over 10 ag/kg of ceruletide attenuated the increase in the response rate induced by methamphetamine (0.5 mg/kg, s.c.). However, ceruletide, at 1-300 ug/kg, did not significantly enhance the response and/or avoidance-decreasing effects of chlorpromazine (1 mg/kg, s.c.), haloperidol (0.1 mg/kg, s.c.), pilocarpine (4 mg/kg, s.c.) and N6-(L-2-phenylisopropyl)-adenosine (0.1 mg/kg, s.c.), but rather tended to reduce the avoidance-decreasing effect of chlorpromazine and pilocarpine at 1-100 fig/kg.

Differential Antagonism of the Stimulant Effects of MK-801 and Methamphetamine by Ceruletide: Evaluation by Discrete Shuttle Avoidance Response in Mice.

“…This re sult indicates the differential characteristics be tween MK-801 and methamphetamine-in duced enhancement of the dopaminergic trans mission. This may be also supported by the facts that ceruletide can completely inhibit the MK-801-induced increase in the mouse's ambulatory activity and the response rate, although it only partially reduced the behavior stimulation by methamphetamine even at large doses (up to 10,ug/kg), and there was no clear dose-effect relationship in the interaction between ceruletide and methamphetamine as demonstrated in the present and previous studies (6,7). MK-801, at 0.1 mg/kg, did not potentiate the stimulant effect of methamphet amine by means of the present avoidance situation and ambulatory activity in mice (un published data, H. Kuribara).…”

“…A preliminary experiment and the previous studies (6,7) demonstrated that the inhibitory action of ceruletide on the ambulation and response-increasing effects of methamphet amine appeared within a few min, and almost the same inhibitory action persisted for longer than 3 hr but not for 24 hr. Therefore, the drug administrations, both in the single and combined administration tests, were conducted immediately before the sessions, and there after the avoidance response of each mouse was observed for 30 min.…”

“…The systemic administration of this pep tide, at over 10 ,ug/kg, significantly reduced the ambulation-increasing and response-in creasing effects of methamphetamine (0.5-2 mg/kg) (6,7). In particular, the shuttle avoid ance was more convenient than the ambula tory activity for detecting the interaction be tween a low dose of methamphetamine and ceruletide.…”

“…The experimental apparatus (experimental chamber, behavior-controlling and data-re cording apparatus; GT-8450, De CARES GT M5 and TIDP-10, respectively; O'Hara & Co.) were the same as those used in our pre vious study (7). The temporal parameters of discrete avoidance schedule were an intertrial interval of 25 sec and a warning duration of 5 sec.…”

Stimulatory Effects of HSR-803 on Ileal Motor Activity

“…In this study, we further evaluated the characteristics of the CNS stimulant effects of methamphetamine, MK-801 and ketamine through combined administration with the selective dopamine D1 and D2-antagonists SCH 23390 (10,11) and YM-09151-2 (12), respectively, by means of discrete shuttle avoidance in mice. Shuttle avoidance has been empirically considered to be convenient for detect ing both the behavioral stimulant and depressant actions of drugs (13).…”