Brain research
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We sought to determine whether chronic vasospasm following subarachnoid hemorrhage (SAH) would abolish the cerebral blood flow (CBF) autoregulation in anesthetized Sprague-Dawley rats. SAH was induced by intracisternal injection of autologous blood; in control animals saline was injected instead. CBF was measured 48 h after SAH, that is during chronic vasospasm, by laser-Doppler flowmetry over the frontal cortex under condition of hypertension (SAH, n = 6; control, n = 8) or hypotension (SAH, n = 6; control, n = 6). ⋯ SAH 10.0 +/- 1.05 mmHg, n = 5) 48 h after SAH was induced. These results indicate that, during chronic vasospasm, SAH does not abolish the autoregulation process but raises its lower and upper blood pressure limits. The capacity of spastic cerebral arteries to dilate in case of hypotension decreased, while their tolerance to hypertension increased.
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Two studies were designed to document neuronal colocalization of androgen receptor immunoreactivity and mating-induced Fos immunoreactivity (AR-ir, Fos-ir) in brain of male rats and to examine the extent to which limbic and midbrain neurons that project to the preoptic area are androgen sensitive and activated by mating. Brains from male rats, killed 1 h after ejaculating with receptive females, were examined for Fos-ir and AR-ir and compared with those from control rats not given access to females. PG21 anti-AR and anti-c-fos primary antibodies were visualized by fluorescence microscopy using cyanine-conjugated and fluorescein-conjugated secondary antibodies. ⋯ Fluorogold-containing neurons were present in dMEA and CTF as well as in other hypothalamic and limbic regions known to project to the MPN. In dMEA and CTF, nuclear colocalization of AR-ir and mating-induced Fos-ir was present in a proportion of FG-containing neurons. Sexually relevant information may be carried through the brain by an interconnected network of hormone-sensitive neurons.
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Antagonists of NMDA glutamate receptors have been shown to alleviate neuropathic pain in rats and humans. However, NMDA antagonists can cause significant side effects ranging from behavioral disturbances to injury of neurons in the posterior cingulate/retrosplenial (PC/RS) cortex. We have found that alpha-2 adrenergic agonists prevent the PC/RS neurotoxic side effects of NMDA antagonists. ⋯ In separate experiments on normal unoperated rats, we found that clonidine (0.05 mg/kg s.c.) counteracted the hyperactivity induced by MK-801 (0.05 mg/kg s.c.) and returned activity levels to a normal range. These findings signify that clonidine, which does not specifically relieve neuropathic pain, can potentiate the neuropathic pain-relieving action of MK-801, while also protecting against neurotoxicity and hyperactivity side effects of MK-801. The potentiation is of a sufficient magnitude that it permits cutting the MK-801 dose requirement in half, thereby achieving prolonged neuropathic pain relief while doubling the margin of safety against any type of side effect that might be mediated by blockade of NMDA receptors.
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In vivo microdialysis was used to compare the effects of serotonergic drugs on morphine- and cocaine-induced increases in extracellular dopamine (DA) concentrations in the rat nucleus accumbens (NAc). Systemic administration of the 5-HT2A/2C agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (2.5 mg/kg, s.c. ) prevented the increase in extracellular DA in the NAc produced by morphine (5 mg/kg, i.p.). In contrast, this dose of DOI had no effect on the ability of cocaine (10 mg/kg, i.p.) to increase extracellular DA concentrations in the NAc. ⋯ In order to determine if inhibition of the firing of 5-HT neurons contributes to the serotonin agonist-mediated inhibition of morphine-induced accumbens DA release, rats were pretreated with the 5-HT1A agonist, 8-OHDPAT. At a dose of 100 microg/kg (sc), 8-OHDPAT did not interfere with morphine's ability to increase DA concentrations in the NAc. These results suggest that the activation of 5-HT2C receptors selectively inhibits morphine-induced DA release in the NAc in a manner which is independent of the inhibition of 5-HT neurons.
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Comparative Study
The effect of morphine on responses of mediodorsal thalamic nuclei and nucleus submedius neurons to colorectal distension in the rat.
In halothane-anesthetized rats, we characterized the responses of single neurons in the nuclei of medial thalamus (MT), specifically the mediodorsal thalamic nucleus (MD) and the nucleus submedius (Sm), to a noxious visceral stimulus (colorectal balloon distension, CRD), and studied the effects of intravenous morphine (Mor) on these responses using standard extracellular microelectrode recording techniques. 62 MD and 46 Sm neurons were isolated on the basis of spontaneous activity. 47 of the MD neurons (76%) responded to CRD, of which 70% had excitatory and 30% had inhibitory responses. 38 of the Sm neurons (83%) responded to CRD, of which 89% had excitatory and 11% had inhibitory responses. Responses of MD and Sm neurons excited by CRD were related significantly to distension pressure (20-100 mmHg), with maximum excitation occurring at 60 and 100 mmHg, respectively. MD neurons inhibited by CRD also had graded responses to graded CRD, with maximum inhibition occurring at 80 mmHg. ⋯ V.) reversed the effects of Mor. Mor and naloxone had no effects on spontaneous activity. These data support the involvement of MD and Sm neurons in visceral nociception, and are consistent with a role of Sm in affective-motivational, and MD in both sensory-discriminative and affective-motivational aspects of nociception.