Neuroscience
-
Neuropeptide plasticity in the gracile nucleus is thought to play a role in the development of neuropathic pain following nerve injury. Two weeks after chronic constriction injury of adult rat sciatic nerve, galanin, neuropeptide Y and calcitonin gene-related peptide immunoreactivities were increased in fibers and cells in the gracile nucleus ipsilateral to injury. At the electron microscopic level, this increased neuropeptide immunoreactivity was localized in myelinated axons, boutons, dendrites, neurons and glial cells. ⋯ However, no neuropeptide Y, galanin and calcitonin gene-related peptide messenger RNA was detected in the injured side gracile nuclei by in situ hybridization. These results show that partial nerve injury to the sciatic nerve induces increases in the content of galanin, neuropeptide Y and calcitonin gene-related peptide immunoreactivities in synaptic terminals within the gracile nucleus, which suggests that there may be increased release of these neuropeptides following sensory or spontaneous stimulation of large-diameter primary afferents following partial nerve injury, perhaps one mechanism involved in neuropathic pain. We also show an apparent transfer of these neuropeptides to the cells of the gracile nucleus, both neurons and glial cells, an intriguing phenomenon of unknown functional significance.
-
We have analysed some behavioral, neuroendocrine and serotonergic consequences of a single (30-min) social defeat followed by 14-18 h of sensory contact with the aggressor, in Lewis rats, an inbred strain highly sensitive to chronic social stressors [Berton O. et al. (1998) Neuroscience 82, 147-159]. In addition, we have investigated how the aforementioned consequences are affected by pretreatment with the selective serotonin reuptake inhibitor, fluoxetine (7.5 mg/kg/day for 21 days). A single social defeat triggered hypophagia and body weight loss, and increased anxiety in the elevated plus-maze. ⋯ Except for a decrease in midbrain serotonin transporter density, fluoxetine did not affect the other serotonergic indices analysed herein, i.e. serotonin-1A and serotonin-2A receptor densities, serotonin synthesis/metabolism. A single social defeat in Lewis rats produces behavioral and endocrine alterations that may model some aspects of human anxiety disorders. In this paradigm, prior fluoxetine treatment is endowed with adaptive behavioral, and possibly neuroendocrine, effects without affecting the key elements of central serotonergic systems analysed herein.
-
We previously presented evidence [Nagy et al. (1997) Neuroscience 78, 533-548] that, in addition to their ubiquitous expression of connexin43, astrocytes produce a second connexin suggested to be connexin30, a recently discovered member of the family of gap junction proteins. A connexin30 specific antibody was subsequently developed and utilized here to confirm and extend our earlier observations. On western blots, this antibody detected a 30,000 mol. wt protein in rat, mouse, cat and human brain, and exhibited no cross-reaction with connexin43, connexin26 or any other known connexins expressed in brain. ⋯ In contrast to regional connexin43 expression, diencephalic and hindbrain areas exhibited considerably greater expression than forebrain areas, subcortical perivascular astrocytic endfeet were more heavily labelled for connexin30, white matter tracts such as corpus callosum, internal capsule and anterior commissure were devoid of connexin30, and appreciable levels of connexin30 during development were not seen until about postnatal day 15. These results indicate that connexin30 is expressed by gray, but not white matter astrocytes, its distribution is highly heterogeneous in gray matter, it is co-localized with connexin43 at astrocytic gap junctions where it forms homotypic or heterotypic junctions, and its emergence is delayed until relatively late during brain maturation. Taken together, these results suggest that astrocytic connexin30 expression at both regional and cellular levels is subject to regulation in adult brain as well as during brain development.
-
Extracellular levels of dopamine are increased in response to systemic administration of cocaine in several brain areas including the nucleus accumbens and medial prefrontal cortex. While the cocaine-induced increase in extracellular dopamine levels in the nucleus accumbens is augmented after repeated daily cocaine, the response of extracellular dopamine levels in the medial prefrontal cortex is attenuated. Since dopamine in the medial prefrontal cortex has an inhibitory effect on nucleus accumbens dopamine levels and locomotor activity, the role of medial prefrontal cortex dopamine tolerance in the expression of sensitized locomotor behavior was further examined by injection of D-amphetamine sulfate into the prelimbic portion of the medial prefrontal cortex just prior to cocaine challenge in cocaine-sensitized rats. ⋯ The results suggest that in rats sensitized to cocaine, decreased medial prefrontal cortex dopamine levels in response to cocaine challenge may contribute to behavioral sensitization. Furthermore, the data indicate the possibility that there is an optimal range at which medial prefrontal cortex amphetamine exerts maximal behavioral inhibition. These findings implicate a role for decreased cortical control in producing sensitized behavioral responding to cocaine.
-
An understanding of the interaction between oestrogen and the nitric oxide synthase/nitric oxide system is important for determining the roles of nitric oxide in central nervous control of osmotic homeostasis and certain aspects of reproduction. The effects of oestrogen on nitric oxide synthase and nitric oxide synthase activity were investigated in the magnocellular neurosecretory system. Ovariectomized female rats were injected subcutaneously with 17beta-estradiol benzoate either 10 microg daily for four days (short-term low-dose) or 200 microg daily for 21 days (long-term high-dose). ⋯ Long-term high-dose oestrogen treatment also had no effect on nitric oxide synthase gene expression or immunoreactivity, but caused a reduction of the proportion of NADPH-diaphorase-positive neurons in the supraoptic nucleus and a reduction in the intensity of this histochemical staining. Qualitatively similar changes were observed in the magnocellular part of the paraventricular nucleus. The results provide, for the first time, evidence of a complex interaction between oestrogen and nitric oxide synthase in the neuroendocrine system in which nitric oxide synthase activity is regulated differently in the magnocellular cell bodies and axonal terminals and in which the activity of the enzyme rather than its expression is controlled.