Electroencephalographic and Convulsive Effects of Binge Doses of (+)- Methamphetamine, 5-methoxydiisopropyltryptamine, and (±)-3,4- Methylenedioxymethamphetamine in Rats

Abstract

The abuse of drugs such as methamphetamine (MA), 3,4-methylenedioxymethamphetamine (Ecstasy, MDMA), and 5-methoxydiisopropyltryptamine (5-MeO-DIPT; Foxy) is global. Symptoms from taking these drugs include tachycardia, agitation, hyperpyrexia, and sometimes seizures. We compared the EEG effects of these drugs in male Sprague-Dawley rats (~300 g) implanted with cortical electroencephalographic (EEG) electrodes prior to testing. Animals received four subcutaneous injections of MA, MDMA, or Foxy (10 mg/kg each as freebase, administered every 2 h), or saline as these doses produce lasting effects on learning, memory, and monoamines. EEG tracings were recorded before, during, and after treatment. Animals receiving MDMA showed no significant EEG abnormalities or myoclonus. MA treatment resulted in myoclonic activity and in brief (<10 s) EEG epileptiform activity in ~50% of the rats. Longer seizure activity (10 s to 5 min) was recorded in some MA-treated rats following the third and fourth doses. The onset of myoclonic activity following Foxy treatment occurred shortly after the first dose. All rats receiving Foxy showed seizures by the second dose and this continued throughout the treatment regimen. The results show that binge doses of MA and MDMA, which mimic the neurochemical changes seen in chronic users, increase EEG abnormalities after MA but not after MDMA. While the neurochemical effects of Foxy are not known in humans, this drug causes severe EEG abnormalities and overt seizures in 100% of tested animals.