Dopaminergic Effects of Isobutyl Nitrite, Isoamyl Nitrite and Butyl Nitrite

Alkyl nitrites have been problematic worldwide due to their recreational use. Although there is a lack of scientific information on their action on the central nervous system (CNS), many anecdotal reports and case studies have inferred the CNS actions of alkyl nitrites. The objective of this study was to investigate the effects of alkyl nitrites on the CNS, especially focusing on the dopaminergic system. Locomotor activity was measured in rats after treatment with three representative alkyl nitrites (isobutyl nitrite, isoamyl nitrite, and butyl nitrite) at several doses to determine the psychostimulating dose of the test substances. Then, a dopamine receptor antagonist, haloperidol, was administered to the animals before a psychostimulating dose of the test substances in order to evaluate the involvement of the dopaminergic system in the locomotor effects of alkyl nitrites. Locomotor activity was significantly increased (to approximately 1.5-2.5-fold that of the control group) in rats treated with 5 mg/kg of the test substances. Stimulated locomotor activity was significantly inhibited (approximately 1.5-2.5-fold reduction relative to the haloperidol-free group) following pre-treatment with haloperidol (0.1 mg/kg). The locomotor effects of the three alkyl nitrites are likely mediated by dopamine receptors, implying that alkyl nitrites increase dopamine levels in the CNS. Our results provide additional scientific evidence in support of controlling alkyl nitrites as psychoactive substances.