5-MeO-AMT, a tryptamine used recreationally for its hallucinogenic and mood-elevating effects, triggers head-twitch response (HTR) in mice through activation of serotonin receptor 2a (5-HTR2a) in the prefrontal cortex. Acute administration at doses 0.3–10 mg/kg produced HTR, but repeated dosing led to tolerance. The 5-HTR2a antagonist ketanserin blocked the response. The drug increased 5-HTR2a mRNA and induced PKC-γ phosphorylation in the prefrontal cortex. 5-MeO-AMT did not produce locomotor sensitization, conditioned place preference, or self-administration, suggesting low abuse potential.
The substituted phenethylamines MAL and BOD have different abuse potentials. MAL produced psychostimulant effects, locomotor sensitization, and was self-administered by rats, indicating reinforcing properties. Both drugs induced conditioned place preference in mice, which was blocked by dopamine receptor antagonists, and both altered dopamine receptor D1 and D2 protein expression in the nucleus accumbens, tyrosine hydroxylase and dopamine transporter in the ventral tegmental area, increased dopamine levels in the nucleus accumbens, and enhanced delta and gamma brain wave activity. BOD caused locomotor depression and lacked rewarding and reinforcing effects, suggesting little to no capability to engender compulsive behavior despite its dopaminergic alterations.