Relationships between oxygen changes in the brain and periphery following physiological activation and the actions of heroin and cocaine

Abstract

Using two-sensor electrochemical recordings in freely moving rats, we examined the relationship between physiological and drug-induced oxygen fluctuations in the brain and periphery. Animals chronically implanted with oxygen sensors in the nucleus accumbens (NAc) and subcutaneous (SC) space were subjected to several mildly arousing stimuli (sound, tail-pinch and social interaction) and intravenous injections of cocaine and heroin. Arousing stimuli induced rapid increases in NAc oxygen levels followed by and correlated with oxygen decreases in the SC space. Therefore, cerebral vasodilation that increases cerebral blood flow and oxygen entry into brain tissue results from both direct neuronal activation and peripheral vasoconstriction, which redistributes arterial blood from periphery to the brain. The latter factor could also explain a similar pattern of oxygen responses found in the substantia nigra reticulata, suggesting hyperoxia as a global phenomenon with minor structural differences during early time intervals following the stimulus onset. While arousing stimuli and cocaine induced similar oxygen responses in the brain and SC space, heroin induced a biphasic down-up brain oxygen fluctuation associated with a monophasic oxygen decrease in the SC space. Oxygen decreases occurred more rapidly and stronger in the SC space, reflecting a drop in blood oxygen levels due to respiratory depression.

Functional role of peripheral vasoconstriction: not only thermoregulation but much more

“…This comparison revealed that both tail-pinch and social interaction induced rapid oxygen increases, similar in their time-course in the NAc and SNr [28] (Fig. 6, Ref.…”

“…5, Ref. [28]). Moreover, these changes are very tightly correlated (r = -0.76 and -0.92 for tail-pinch and social interaction, respectively).…”

“…To provide more direct proof for the mechanisms responsible for physiological increases in brain oxygen and glucose, we recently developed a two-sensor recoding technology where one oxygen sensor was implanted in the brain structure (NAc) and another in the SC space [28]. Using this approach, we found that oxygen changes in the NAc and SC space induced by both tail-pinch and social interaction occurred in opposite directions, rapidly increasing in the brain and decreasing in the periphery (Fig.…”

“…Changes in oxygen in the NAc and subcutaneous space elicited by both arousing stimuli show a significant opposite correlation (r = -0.76 and 0.92 for tail-pinch and male-to-male social interaction. Original data were published in [28].…”

“…To determine whether NE increases CFB and entry of oxygen and glucose in brain tissue, we examined changes in Original data were published in [28,37].…”