Effects of Inhalants on Specific Neurotransmitter Systems

There are few reports on the effects of nitrous oxide on dopaminergic neurotransmission. A study in mice showed that nitrous oxide inhalation produced a significant increase in locomotor activity that was antagonized in a dose-dependent fashion by the dopamine synthesis inhibitor a-methyl-/)-tyrosine (Hynes and Berkowitz 1983). Moreover, administration of the D2 antagonist haloperidol also reduced the locomotor activity induced by nitrous oxide (Hynes and Berkowitz 1983). These results suggest that excitatory effects induced by nitrous oxide may be also mediated by dopaminergic neurotransmission. However, other studies have reported that exposure to nitrous oxide resulted in decreased dopamine release by neurons in the striatum (Balon et al. 2002 Turle et al. 1998). 

Although, to our knowledge, the effects of inhalation of amyl nitrite or butyl nitrite on glutamatergic neurotransmission have not been studied, NO, the potent compound that mediates the peripheral effects of nitrites in blood vessels, if released in the CNS when nitrites are inhaled, may potentially affect the glutamatergic system. NO has been reported to act directly on the postsynaptic NMDA receptor, where it can increase or decrease NMDA-mediated currents and subsequent calcium influx (Aizenman et al. 1990 Dingledine et al. 1999 Manzoni et al. 1992). 

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