Neuroscience
-
The purpose of the present study was to investigate whether differences in the function of monoaminergic systems could account for the variability in attention and impulsive behaviour between rats tested in the five-choice serial reaction time task in a model of attention deficit hyperactivity disorder. The ability of a rat to sustain its attention in this task can be assessed by measuring choice accuracy (percent correct responses) to visual stimuli, whereas the percentage of premature responses indicates the level of impulsivity. Following training with the five-choice serial reaction time task, rats were decapitated and brain pieces taken for neurochemical determination. ⋯ According to the regression analysis, a negative correlation existed between the left frontal cortex 5-hydroxyindoleacetic acid/5-hydroxytryptamine and choice accuracy, and a positive correlation was observed between 3,4-dihydroxyphenylacetic acid/dopamine ratio and choice accuracy on the opposite hemisphere. Additionally, right frontal cortex serotonin utilization was found to correlate positively with the proportion of premature hole responses and this relation accounted for about 24% of the variability in this index of impulsivity between animals. These data indicate that frontal cortex dopamine and serotonin play an important role in the modulation of attention and response control.
-
Stimulation of the cornea activates neurons in two distinct regions of the spinal trigeminal nucleus: at the transition between trigeminal subnucleus interpolaris and subnucleus caudalis and at the transition between trigeminal subnucleus caudalis and the upper cervical spinal cord as estimated by expression of the immediate early gene, c-fos. To determine if receptors for substance P or neurokinin A, neurokinin 1 and neurokinin 2 receptors, respectively, contribute to the production of Fos-positive neurons in these brainstem regions, receptor-selective antagonists were given intracerebroventricularly 15 min prior to stimulation of the cornea in anesthetized rats. The number of Fos-positive neurons produced in superficial laminae at the trigeminal subnucleus caudalis/cervical cord transition by application of the selective small fiber excitant, mustard oil, to the corneal surface was reduced by the neurokinin 1 receptor antagonist, CP99,994 (5-100 nmol, i.c.v.) and the neurokinin 2 receptor antagonist, MEN10,376 (0.01-1.0 nmol, i.c.v.). ⋯ Tachykinin receptor antagonists did not reduce the number of Fos-positive neurons produced at the subnucleus interpolaris/subnucleus caudalis transition. The elevation in plasma concentration of adrenocorticotropin, but not the increases in arterial pressure or heart rate, evoked by corneal stimulation was prevented by pretreatment with CP99,994 or MEN10,376 at doses lower than those needed to reduce c-fos expression. The results indicate that receptors for substance P and neurokinin A contribute to the transmission of sensory input from corneal nociceptors to brainstem neurons in trigeminal subnucleus caudalis and to increased activity of the hypothalamo-pituitary axis that accompanies acute stimulation of the cornea.
-
Glial cell line-derived neurotrophic factor (GDNF) has two receptors, receptor-tyrosine kinase c-ret and glycosylphosphatidylinositol-linked cell surface receptor GDNFRalpha. Kainate-induced seizures, a widely studied model of neuronal plasticity and human epilepsy, have been shown to increase gene expression of several trophic factors, including GDNF, in the rat hippocampus. Here we show that systemic kainate-induced excitation leads to a transient increase of both c-ret and GDNFRalpha messenger RNAs in the rat brain. ⋯ GDNFRalpha messenger RNA was prominently induced in the dentate gyrus of the rat hippocampus, less in the habenular and reticular thalamic nuclei and cerebral cortex as revealed by in situ hybridization. C-ret transcripts were induced in the hilus of the hippocampus, several thalamic and amygdala nuclei and in superficial layers of the piriform cortex. These data suggest that GDNF and its receptors may play a local role in neuronal plasticity and in neuronal protection following epileptic insults.
-
The effect of chronic spinal cord transection on neurofilament immunoreactivity and capsaicin sensitivity of L6 and S1 dorsal root ganglion neurons innervating the urinary bladder was examined using an antibody (RT97) against 200,000 mol. wt subunit of neurofilament protein and a cobalt uptake assay, respectively. Bladder afferent neurons labelled by axonal transport of a fluorescent dye (Fast Blue) injected into the bladder wall were identified in sections of intact dorsal root ganglia and among dissociated neurons in short-term culture. Approximately two thirds of bladder afferent neurons from spinal intact rats were neurofilament-poor (i.e. ⋯ Immunoreactivity to neurofilament protein which occurred in 32% of bladder afferent neurons in spinal intact animals was detected in a larger percentage (56% to 62%) of neurons from spinal transected animals. Conversely, the population of capsaicin-sensitive dissociated neurons was reduced from 55% in spinal intact rats to 38% in spinal transected rats. These results indicate that spinal cord injury induces functional and morphological plasticity in C-fibre visceral afferent neurons innervating the urinary bladder.
-
Systemic nicotine enhances burst firing of dopamine neurons in the ventral tegmental area and dopamine release in the nucleus accumbens, mainly via stimulation of nicotinic acetylcholine receptors in the ventral tegmental area. Given that both the neuronal activity of mesolimbic dopamine neurons and terminal dopamine release are regulated by excitatory amino acid inputs to the ventral tegmental area and that nicotine facilitates glutamatergic transmission in brain, we investigated the putative role of ionotropic glutamate receptors within the ventral tegmental area for the effects of nicotine on dopamine release in the nucleus accumbens using microdialysis, with one probe implanted in the ventral tegmental area for drug application and another in the ipsilateral nucleus accumbens for measuring dopamine, in awake rats. Systemic nicotine (0.5 mg/kg, s.c.) and infusion of nicotine (1.0 mM) into the ventral tegmental area increased dopamine output in the nucleus accumbens. ⋯ Infusion of either antagonist (0.3 or 1.0 mM) into the ventral tegmental area did not affect basal dopamine levels, whereas infusion of 2-amino-5-phosphonopentanoic acid, but not 6-cyano-7-nitroquinoxaline-2,3-dione, starting 40 min before nicotine injection dose-dependently attenuated the nicotine-induced increase in accumbal dopamine release. Concurrent intrategmental infusion of 2-amino-5-phosphonopentanoic acid and nicotine decreased nicotine-induced dopamine release in the nucleus accumbens. These results indicate that the stimulatory action of nicotine on the mesolimbic dopamine system is to a considerable extent mediated via stimulation of N-methyl-D-aspartate receptors within the ventral tegmental area.