Brain research
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The influence of midthoracic spinalization on thermally and mechanically induced spinal withdrawal reflex responses was studied in the rat. There were three experimental groups of rats: healthy controls, rats with a spinal nerve ligation-induced unilateral neuropathy, and rats with a carrageenan-induced inflammation of one hindpaw. Tail flick response was induced by radiant heat. ⋯ In contrast, spinal withdrawal responses induced by noxious cold or mechanical stimulation were significantly suppressed following spinalization. The spinalization-induced facilitatory effects as well as inhibitory ones on spinal reflexes were enhanced in inflamed/neuropathic animals. The results indicate that the tonic descending control of spinal nocifensive responses varies depending on the submodality of the test stimulus, the segmental level of the reflex (tail vs. hindlimb), and on the pathophysiological condition.
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A new simple behavioral method was used for the evaluation of the anti-hyperalgesic properties of tramadol in the rat. At the lowest dose (1.25 mg/kg i.p.), tramadol did not modify thermal nociceptive thresholds, but it was able to prevent and block thermal hindpaw hyperalgesia induced by the tail injection of formalin. Our results provide evidence that tramadol blocks hyperalgesic behaviors without altering nociception, suggesting that this analgesic drug might represent a valid agent against central sensitization.
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Comparative Study
Normal and drug-induced locomotor behavior in aging: comparison to evoked DA release and tissue content in fischer 344 rats.
The consequences of aging on dopamine (DA) regulation within the nigrostriatal and mesolimbic systems were investigated with a combination of behavioral, in vivo electrochemical, and high-performance liquid chromatography measurements using 6-, 12-, 18- and 24-month old male Fischer 344 (F344) rats. Spontaneous locomotor testing demonstrated that aged (18- and 24-month) rats moved significantly less and at a slower speed than younger (6- and 12-month) animals. Additionally, systemic injection (intraperitoneal) of the DA uptake inhibitor, nomifensine, was significantly less efficacious in augmenting the locomotor activity of aged rats compared to the younger animals. ⋯ In addition, the duration of the electrochemical DA signals recorded within the striatum of 24-month old rats was twice that in the younger animals (6- and 12-month). Whole tissue measurements of DA and DA metabolites suggest age-related deficits in locomotion and DA release were not related to decreases in the storage or synthesis of DA within the striatum, nucleus accumbens, substantia nigra, ventral tegmental area or medial prefrontal cortex. Taken together, these results indicate age-dependent deficits in movement are related to the dynamic properties of DA release and not static measures of DA content.
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Previous studies in rats have shown that spinal morphine loses potency and efficacy to suppress an acute nociceptive stimulus applied to the tail or the paw following injury to peripheral nerves by tight ligation of the L5/L6 spinal nerves. Additionally, intrathecal (i.th.) morphine is ineffective in suppressing tactile allodynia at fully antinociceptive doses in these animals. The molecular basis for this loss of morphine potency and efficacy in nerve injury states is not known. ⋯ At these spinal segments, mu opioid receptors were decreased in laminae I and II. The data indicate that the loss of mu opioid receptors are highly localized and may contribute to the loss of morphine activity involving input at these spinal segments (e.g., foot-flick response). On the other hand, the lack of a generalized loss of opioid mu receptors across spinal segments makes it unlikely that this is the primary cause for the loss of potency and efficacy of mu opioids to suppress multi-segmental reflexes, such as the tail-flick response.
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Besides the dopaminergic afferent projection system, calbindin (CALB)- and calretinin (CR)-immunoreactive fibres of intrinsic and extrinsic origin represent the most abundant axonal categories in the rat striatal and lateral septal areas. The question arises whether or not they may represent separate populations, or whether they form subgroups which co-express more than one of these antigens. Therefore, the present study is focused on the distribution patterns of the axons single-immunolabelled by the catecholaminergic marker tyrosine hydroxylase (TH), and on TH-immunoreactive axons displaying also CR- and/or CALB-immunoreactivity in double-immunostained sections. ⋯ The TH-immunoreactive fibres in the striatal patches displaying CR- but not CALB-immunoreactivity may originate mainly from neurons in the ventral tier of pars compacta (SNC) and from the pars reticulata of substantia nigra (SNR) which show identical cytochemical properties. Axons in the matrix of CP and the accumbal core as well as in the islands of Calleja single-labelled by the TH-immunoreactivity or additionally containing CALB and CR may originate from neurons in the dorsal tier of mesencephalic nuclei like SN, pars compacta and ventral tegmental area. CR-containing TH-immunoreactive basket-like axon terminations in the dorsal lateral septal nucleus are likely to originate either from mesencephalic nuclei or from the supramammillary region.