Behavioral study on an antitussive and expectorant, and of its constituents. II. Effects on ambulatory activity after repeated administration, and a modification of the methamphetamine sensitivity in mice
Kuribara, H.; Tadokoro, S.
Arukoru Kenkyu to Yakubutsu Izon 24(5): 430-438
1989
ISSN/ISBN: 0389-4118 PMID: 2624571 Document Number: 344840
Effects of repeated oral administration of a commercial preparation of antitussive and expectorant, BRON-W Solution (SS Pharmaceut., BRON; 10ml/kg), and of single and combination of dihydrocodeine (2HCOD; 10mg/kg), methylephedrine (MEPH; 20 mg/kg), caffeine (CAF; 20.6mg/kg) and chloropheniramine (CPA; 4mg/kg) were investigated by means of ambulatory activity in mice. The drug doses tested were identical with those in BRON 10ml/kg. The drug administration was conducted 5 times at intervals of 3-4 days. Furthermore, 4 days after the final treatments, all mice were given methamphetamine 2 mg/kg s.c. In the single administration regimen of individual drugs, only CAF significantly increased the ambulatory activity. However, there was no significant change in the ambulation-increasing effect of CAF after the repeated administration. The other 3 drugs failed to elicit any marked change in the activity throughout the 5 times administration. Such the repeated administration of the individual drugs induced no significant change in the sensitivity to the ambulation-increasing effect of methamphetamine. BRON and BRON-corresponding combination of 4 drugs increased the ambulatory activity in the 1st administration, and the ambulation-increasing effect was progressively enhanced by the repeated administration of these preparations. On the other hand, although CAF-containing solutions significantly increased the ambulatory activity in the 1st administration, the proportions of the changes in the ambulatory activity during the repeated administration regimen were different from that observed after BRON. The combined administration of 2HCOD + MEPH + CPA failed to increase the ambulatory activity in the 1st administration, but significantly increased it in the 2nd and 3rd administration, then elicited again no significant increase in the activity in the 4th and 5th administration. The mice that experienced repeated administration of BRON and 2HCOD-containing solutions showed significantly higher ambulatory activity counts than saline-treated or drug-naive control mice when methamphetamine was administered. The present results suggest that, by means of the ambulatory activity in mice, CAF plays the most important role in the effect of BRON, and that other 3 drugs modify the effect of CAF. Furthermore, it is considered that repeated abuse of BRON may easily elicit an increase in sensitivity to methamphetamine, i.e., a development of amphetamine psychosis.