Neuroscience
-
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.
-
In human neocortical slices obtained during epilepsy surgery, sharp waves have been described to appear spontaneously, the shape of which met all criteria of epileptiform field potentials. In the present investigation, the current sinks and sources underlying these potentials were analysed. The cortical tissue used in the present study was a small portion of the tissue blocks excised for treatment of pharmacoresistant focal epilepsy. ⋯ The results suggest that the supragranular layers, especially layer II, change qualitatively in functional organization in slices showing spontaneous discharges. We think that this special feature represents the function of the upper layers and can be blocked by bicuculline. This interpretation is supported by the observation that ictal discharges normally started in the upper layers in spontaneous and non-spontaneous slices, except for spontaneous slices with bicuculline, where the zone initiating discharges was translocated to deeper layers.
-
We propose that the primary afferent depolarization that follows GABA(A) receptor activation in the spinal cord also occurs in the periphery. As evidence, the present study localizes beta2/beta3 and alpha1 subunits of the GABA(A) receptor on 10-14% of the unmyelinated primary afferents axons in the glabrous skin of the cat paw. Behavioral studies demonstrate that local peripheral injection of the GABA(A) agonist muscimol at a low concentration (2.0 microM) attenuates, and at a high concentration (1 mM) enhances, formalin-induced nociceptive behaviors. ⋯ Higher concentrations of muscimol further depolarize GABA(A) receptor-containing terminals, which then initiates action potentials in nociceptors analogous to the appearance of dorsal root reflexes that arise following activation of GABA(A) receptors on central primary afferent terminals. These latter events reverse the analgesic effects of GABA(A) ligands and lead to potentiation of nociceptive input. Thus, the present study provides anatomical and behavioral evidence supporting a bimodal role for GABA(A) receptors in the modulation of peripheral nociceptive transmission.
-
The present study was carried out to evaluate the effect of morphine, cocaine and ethanol on the density of opioid receptors in the nucleus accumbens and striatum of rat brain. The animals were injected i.p. with morphine in a single dose 20 mg/kg, or twice daily for 10 days in increasing doses of 20-100 mg/kg. Cocaine was administered in a dose of 60 mg/kg/day following the "binge" paradigm, every hour for 3 h, one day (single treatment) or five days (chronic treatment). ⋯ A long-term intake of ethanol solution down-regulates mu opioid receptors in both structures, but has no effect on any type of delta receptors. Thus changes in the particular opioid receptor depend on the type of drug used. Furthermore, the most profound changes are observed after late withdrawal, which may play some role in maintaining the state of dependence.