Absence of synthesis-modulating nerve terminal autoreceptors on mesoamygdaloid and other mesolimbic dopamine neuronal populations

Abstract

The present study sought to map the distribution of dopamine (DA) synthesis-modulating autoreceptors on DA nerve terminals innervating the amygdala and other limbic structures of the rat brain at a level of anatomic resolution (i.e., discrete component nuclei) commensurate with the functional organization of such structures. The biochemically estimated response of mesoamygdaloid and other limbic DA neuronal populations to conditions of minimal (gammabutyrolactone administration or surgical axotomy) and maximal (low-dose apomorphine administration) activation of nerve terminal DA autoreceptors was examined and compared to the response of mesostriatal and mesocortical DA neurons. In contrast to the caudate nucleus, nucleus accumbens, and olfactory tubercle, neither gammabutyrolactone (GBL) nor axotomy increased biochemically estimated DA synthesis (DOPA accumulation) in any of the amygdaloid nuclei, the anterior amygdaloid area, septal nuclei, or subdivisions of the interstitial (bed) nucleus of the stria terminalis. These results indicate that, similar to the medial prefrontal cortex and median eminence, DA synthesis in mesoamygdaloid and other subcortical limbic DA neuronal populations is not under the regulatory influence of tonically active, nerve terminal-localized autoreceptors. Both GBL and axotomy increased DOPA accumulation in the anterior cingulate cortex, but not in allocortical projection fields. In contrast to the differential distribution of DA synthesis-modulating terminal autoreceptors, the end-product inhibition of tyrosine hydroxylase activity appears to be a ubiquitously expressed regulatory property of DA neurons. The decrease in DA metabolism produced by the administration of a low, presumably auto-receptor-selective, dose of apomorphine exhibited a DA neuronal population distribution distinctly unlike that of the aforementioned effects of GBL or axotomy on DOPA accumulation. These results reinforce the DA neuronal population-selective distribution of synthesis-modulating autoreceptors and indicate that nerve terminal-localized autoreceptors are operative in regulating DA synthesis in only a minority of DA-innervated brain structures. Further, the demonstration of such autoreceptors is dependent upon the preparation, pharmacological tools, and functional endpoints chosen for study.