NOREPINEPHRINE FACILITATES THE DEVELOPMENT OF THE MURINE SWEAT RESPONSE BUT IS NOT ESSENTIAL

During development, the sympathetic neurons innervating sweat glands u ndergo a neurotransmitter switch from noradrenergic to cholinergic bet ween postnatal day (P) 4, when the sympathetic neurons first contact t he sweat glands, and P21. Several in vitro experiments suggest that no repinephrine (NE), produced by sympathetic neurons, stimulates sweat g lands to produce a factor that then induces the phenotypic switch, We tested this hypothesis in vivo using dopamine beta-hydroxylase-deficie nt mice (DBH -/-), which are unable to synthesize NE and epinephrine, and tyrosine hydroxylase-deficient mice (TH -/-), which are unable to synthesize any catecholamines. The cholinergic agonist pilocarpine and electrostimulation of the sciatic nerve both elicited a sweat respons e in adult DBH -/- mice that was indistinguishable from the response o f controls, and the cholinergic antagonist atropine effectively blocke d these responses, We did note, however, a 1- to 2-week delay in the a cquisition of the sweat response in DBH -/- mice, Although diminished in magnitude, a sweat response to pilo-carpine was also noted in TH -/ - mice at P21. Immunohistochemistry demonstrated that TH and vasoactiv e intestinal peptide were detectable at P14 and increased to adult lev els by P21 in DBH +/- and DBH -/- mice. These observations indicate th at NE is not essential for the acquisition of the cholinergic phenotyp e, but it may facilitate its postnatal development.