Abstract
The effect of diazepam, haloperidol, MK-801, and propranolol in antagonizing behavioral symptoms induced by lethal doses of cocaine, amphethamine, and methamphetamine were studied in a rat model. Animals were first pretreated IP with potential antagonists, diazepam (2, 5, and 10 mg/kg), haloperidol (5, 10, and 20 mg/kg), propranolol (5, 10, and 20 mg/kg), MK-801 (0.5, 1.0, and 2.5 mg/kg), and then were challenged IP with cocaine (70 mg/kg) (LD85), d-amphethamine (75 mg/kg) (LD100), and methamphetamine (100 mg/kg) (LD90). Diazepam, at all doses, provided significant protection against cocaine- (p≤0.01) and methamphetamine- (p≤0.05) induced seizures and produced a dose-dependent effect against amphetamine-induced seizures. MK-801, at all doses, reduced seizures in all groups (p≤0.01). Propranolol altered the incidence of methamphetamine-induced seizures. Significant protection against cocaine-induced death was afforded by diazepam (p≤0.01) and propranolol (p≤0.05). Significant protection against amphetamine-induced death was provided by haloperidol (all doses, p≤0.1), MK-801 (all doses, p≤0.1), and propranolol (10 and 20 mg/kg, p≤0.1). No agent reduced the incidence of methamphetamine- (50 or 100 mg/kg) induced death. The failure of d-amphetamine antagonists to protect against methamphetamine-induced toxicity and death suggest that different mechanisms of toxicity may exist between these drugs.
Original language | English (US) |
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Pages (from-to) | 745-749 |
Number of pages | 5 |
Journal | Pharmacology, Biochemistry and Behavior |
Volume | 36 |
Issue number | 4 |
DOIs | |
State | Published - 1990 |
Keywords
- Amphetamine
- Cocaine
- Diazepam
- Haloperidol
- Methamphetamine
- MK-801
- Propranolol
ASJC Scopus subject areas
- Biochemistry
- Behavioral Neuroscience
- Pharmacology