A single-day 'binge' dosing regimen of methamphetamine in male mice impaired recognition memory, reduced social behaviors, and increased sensitivity to a hallucinogenic drug that activates serotonin 5-HT2A receptors. The heightened behavioral, molecular, and electrophysiological responses to the hallucinogen were linked to an up-regulation of 5-HT2A receptors in the medial prefrontal cortex, while 5-HT2C and 5-HT1A receptors remained unchanged. These findings suggest that methamphetamine-induced changes in 5-HT2A receptor expression may contribute to psychosis-like behaviors and could inform therapies for methamphetamine-related psychiatric disorders.
N-acetylcysteine (NAC) attenuates hallucinogenic effects caused by activation of the serotonin 5-HT2A receptor, as shown in mice. NAC reduced head twitch responses, expression of c-Fos and Egr-2 in brain regions, and excitatory field potentials in cortical slices induced by the hallucinogenic drug DOI. These effects were reversed by blocking the cystine-glutamate antiporter or the mGluR2 receptor, indicating NAC works by increasing activity of the antiporter followed by activation of mGluR2 receptors. NAC may be a potential therapeutic for hallucinations and psychosis.