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.

Adolescent brain cognitive development (ABCD) study: Overview of substance use assessment methods

“…Human and preclinical evidence demonstrates that other illicit substances are linked with neurocognitive deficits in adolescents and young adults, including cocaine (Cannizzaro et al, 2014; Nuijten et al, 2016; Kaag et al, 2016, 2014; Marhe and Franken, 2014; Rose-Jacobs et al, 2011; Lundqvist, 2010; Meade et al, 2015; Fernández-Serrano et al, 2010; Sim et al, 2007; Rahman and Clarke, 2005; Kober et al, 2016; Verdejo-Garcia et al, 2015; Moreno-López et al, 2015; Ide et al, 2014; Tau et al, 2014; Albein-Urios et al, 2014; Ernst et al, 2000; Mayer et al, 2013), methamphetamine (Buck and Siegel, 2015; Cuzen et al, 2015; King et al, 2010; Scott et al, 2007), MDMA or ecstasy (Medina et al, 2005; Medina and Shear, 2007; Costa et al, 2014; Price et al, 2014; Downey et al, 2015; Halpern et al, 2011; Scholey et al, 2011; McCann et al, 2014, 2008; Jager et al, 2008; de Win et al, 2008), inhalants (Takagi et al, 2011a, 2011b, 2014; Scott and Scott, 2012, 2014), heroin (Zeng et al, 2013; Lundqvist, 2010; Ornstein et al, 2000; Fernández-Serrano et al, 2010), cathinones (Albertson et al, 2016; Patrick et al, 2016), ketamine (Chen et al, 2015; Nagy et al, 2015; Tang et al, 2013; Sun et al, 2014; Morgan et al, 2012a), gamma hydroxybutyrate (Johansson et al, 2014; Sircar et al, 2008; Youn et al, 2015), hallucinogens (lysergic acid diethylamide, phencyclidine, peyote, mescaline, N,N- dimethyltryptamine, alpha-methyltryptamine, or 5-methoxy-N,N-diisopropyltryptamine, psilocybin, or salvia) (Compton et al, 2011; Noworyta-Sokołowska et al, 2016; Graham et al, 2010, 2012; Halpern et al, 2005; Carstairs and Cantrell, 2010; Fickenscher et al, 2006; Mahendran et al, 2016; Ranganathan et al, 2012), and anabolic steroids (Wallin-…”