Potentiation of methamphetamine-induced behavior by Phenytoin in mice: Suppression by propranolol

• Published in: Japanese journal of pharmacology 1983, Vol.33, p.50-50
• Main Authors: Izumi, Kanji, Koja, Takeshi, Shimizu, Takao, Kishita, Chikara, Nomoto, Masahiro, Fukuda, Takeo
• Format: Article
• Language: English
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)60233-7

We investigated effects of various drugs affecting noradrenergic, serotonergic and cholinergic activities upon potentiating action of Phenytoin (PNT) for methamphetamine (MA)-induced behavior in mice. Five min after pretreatment with PNT (10 mg/kg), male adult mice were injected with propranolol, methysergide or atropine or saline 5 min prior to an injection of MA (10 mg/kg). All solutions were administered i.p. Stereotypy and tremor produced by this combination of MA plus PNT were approximately 1.5 and 2.0 times potent, respectively, as compared with those induced by a single injection of MA. MA-induced behavioral responses were individually observed and scored in a photocell chamber allowing simultaneous recording of locomotor activity. Methysergide reduced the scores for stereotypy induced by MA plus PNT only with the highest dose (15 mg/kg), while this serotonin-receptor blocker did not affect the scores for tremor. Atropine (5 mg/kg) did not influence behavior caused by MA plus PNT. Propranolol (1-10 mg/kg) decreased dose-dependently the scores for tremor and stereotypy produced by MA plus PNT. Even with the smallest dose, stereotypy was suppressed significantly. The effects of propranolol accompanied alteration of locomotor activity: the activity did not decrease with time to the same extent as that in control animals probably because stereotypy and tremor were suppressed. Since propranolol (1 mg/kg) was found not to alter the behavioral responses induced by MA alone in separate experiments, the suppressive actions of the μ-adrenoceptor blocker against tremor and stereotypy produced by MA plus PNT may be due to an interaction with PNT in the central nervous system.