Distribution of alpha 2A-adrenergic receptor-like immunoreactivity in the rat central nervous system.

In this study, we analyzed immunohistochemically the distribution of the A subtype of alpha 2-adrenergic receptor (alpha 2A-AR) in the rat central nervous system using light level immunohistochemistry. By using affinity-purified antisera, we found perikaryal labeling was diffuse and/or punctate; immunoreactive puncta were heterogeneous in size and number in a region-specific manner. Dense deposits of immunoreaction product were found associated with neuropil also, particularly in the lateral parabrachial nucleus, locus coeruleus, lateral septum, diagonal band, stratum lacunosum-moleculare of CA1, and various nuclei of the amygdala and extended amygdala. Prominently immunoreactive olfactory structures include the anterior olfactory nucleus and the granular layer of the olfactory bulb. The cortex was generally light to moderately labeled with greater immunoreactivity in the cingulate and insular cortices. alpha 2A-AR-like immunoreactivity was intense in the basal forebrain and continuous from the nucleus accumbens through the substantia innominata and fundus of the striatum. Most immunoreactivity in the diencephalon was restricted to the hypothalamus with light to moderate labeling in the thalamus. Generally light immunoreactivity was observed in midbrain structures. In the pons and medulla, both perikaryal and neuropil labeling were observed. Together with the accompanying paper describing the neural distribution of alpha 2C-AR-like immunoreactivity, our results provide an extensive immunohistochemical cartography of alpha 2-ARs in the adult rat central nervous system.

Chronic imipramine administration alters the activity and phosphorylation state of tyrosine hydroxylase in dopaminergic regions of rat brain.

In the present study the influence of imipramine, a tricyclic antidepressant, on the expression and function of tyrosine hydroxylase (TH) in dopaminergic rat brain regions was examined. Chronic administration of imipramine (18 days) decreased levels of TH enzyme activity in ventral tegmental area (VTA) and substantia nigra (SN), dopaminergic cell body regions, as well as in caudate-putamen (CP), nucleus accumbens (ACB), prefrontal cortex (PFC), and olfactory tubercle (OT), dopaminergic terminal fields. These effects were dependent on chronic drug treatment, as imipramine administration for 1 or 7 days did not significantly influence levels of TH activity in either SN or VTA. In contrast to drug regulation of enzyme activity, chronic imipramine treatment did not decrease levels of TH immunoreactivity in any of the dopaminergic cell body or terminal field regions studied, although levels of TH immunoreactivity were decreased in locus coeruleus (LC) as previously reported. However, imipramine treatment increased levels of TH back phosphorylation in VTA, suggesting that the antidepressant-induced decrease in levels of TH activity is a result of decreased phosphorylation of the enzyme. These results demonstrate that imipramine treatment regulates levels of TH enzyme activity in dopaminergic brain regions, and may account for some of the previously observed effects of these drugs on dopaminergic function. Finally, imipramine regulation of TH enzyme activity in VTA and immunoreactivity in LC was observed in Sprague Dawley, but not Wistar rats, demonstrating that different rat strains exhibit different biochemical responses to antidepressant treatment.