Effects of the designer drug 4-methylamphetamine on core temperature and serotonin levels in the striatum and hippocampus of rats

• Published in: Neuroscience letters Vol. 827; p. 137740
• Main Authors: Gilman, T. Lee, Canfield, Jeremy R., Worst, Travis J., Sprague, Jon E.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 28.03.2024
• Subjects: 4-methylamphetamine; Amphetamine - pharmacology; Amphetamines; Animals; Designer drug; Designer Drugs - pharmacology; Hippocampus; Methamphetamine - pharmacology; N-Methyl-3,4-methylenedioxyamphetamine - pharmacology; Rats; Serotonin; Serotonin - pharmacology; Serotonin Agents - analysis; Serotonin Agents - pharmacology; Striatum; Temperature; Thermogenesis; L-DOP; DEA; Striatum; Thermogenesis; Serotonin; 4-MA; 4-methylamphetamine; 5-HT; Designer drug; Hippocampus; MDMA
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2024.137740

[Display omitted] New psychoactive substances (NPS) are typically synthesized in clandestine laboratories in an attempt to chemically modify already federally regulated drugs in an effort to circumvent the law. Drugs derived from a phenethylamine pharmacophore, such as 4-chloroamphetamine and 3,4-methylenedioxymethamphetamine (MDMA), reliably induce thermogenesis and serotonergic deficits in the striatum and hippocampus of rodents. 4-methylamphetamine (4-MA), a relative newcomer to the NPS scene, was originally investigated in the mid-1900 s as a potential anorexigenic agent. With its phenethylamine pharmacophore, 4-MA was hypothesized to produce similar toxicological alterations as its chemical analogs. In the present study, three doses (1.0, 2.5, and 5.0 mg/kg, ip.) of 4-MA were administered to rats twice daily for two days. Core temperature data were calculated and analyzed as temperature area under the curve (TAUC). On the second day of dosing, a hypothermic response to 4-MA (2.5 and 5.0 mg/kg) was noted between 0.5 and 2.0 h post-treatment. Only the highest dose of 4-MA decreased body weight on the second day of treatment and maintained this reduction in weight for seven days after treatment ceased. None of the doses of 4-MA evaluated significantly altered serotonin levels in the hippocampus or striatum seven days after final treatment. The present findings demonstrate that the 4-methyl substitution to amphetamine generates a pharmacological and toxicological profile that differs from other similar phenethylamine analogs.