Intravenous Cocaine Increases Oxygen Entry into Brain Tissue: Critical Role of Peripheral Drug Actions.

Although it is well established that the direct action of cocaine on centrally located neural substrates is essential in mediating its reinforcing properties, cocaine induces very rapid immediate neural effects that imply cocaine's action on peripheral neural substrates. We employed oxygen sensors coupled with high-speed amperometery to examine the effects of standard cocaine HCl that easily enters the blood-brain barrier and its blood-brain barrier-impermeable methiodide analogue on oxygen levels in the nucleus accumbens in awake, freely moving rats. Both drugs induced strong increases in nucleus accumbens oxygen levels, which displayed similarly short, second-scale latencies and a general similarity with oxygen increases induced by an auditory stimulus. This study provides additional support for the view that the immediate neural effects of intravenous cocaine are triggered via its direct action on peripherally located neural substrates and fast neural transmission to the central nervous system via somatosensory pathways.