Electroencephalographic and convulsive effects of binge doses of (+)-methamphetamine, 5-methoxydiisopropyltryptamine, and (±)-3,4-methylenedioxymethamphetamine in rats.

Binge doses of methamphetamine (MA) cause brief epileptiform brain activity in about half of rats and longer seizures in some, while MDMA produces no significant brain-wave abnormalities or muscle jerks. The drug Foxy (5-MeO-DIPT) triggers seizures in all rats shortly after the first dose, with muscle jerks appearing soon after injection. These effects were observed in male rats implanted with cortical electrodes and given four injections of each drug (10 mg/kg every two hours), a regimen that mimics the neurochemical changes seen in chronic users. The findings indicate that MDMA does not increase EEG abnormalities under these conditions, whereas MA and especially Foxy produce severe brain-activity disturbances.

Study at a glance

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.