Neuroscience
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We used the hot plate test and the formalin test to evaluate the antinociception of choline after i.c.v. or i.v. administration. The analgesic mechanism of choline was also studied. The response latency of mice was significantly prolonged in the hot plate test after choline (90-120 mug/animals) i.c.v. administration in a dose-dependent manner. ⋯ Similarly, coadministration of choline (2 mg/kg) with morphine (0.165 mg/kg) significantly increased the antinociception of morphine in the late phase, but had no effect in the early phase. These results demonstrate that activation of alpha7 nicotinic receptors by choline elicits antinociceptive effects both in an acute thermal pain model and in an inflammatory pain model. Choline holds promise for development as a non-addictive analgesic drug and in reducing the regular dose of aspirin or morphine in inflammatory pain.
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Muscle atonia is a central feature of adult REM sleep which has recently been demonstrated to be a component of sleep in rats as young as 2 days of age (P2). The neural generation of atonia, which depends on mesopontine and medullary structures, is not fully understood in adults and has never been described in infants. In the present experiments we used electrical stimulation in decerebrated pups to identify an inhibitory area within the medial medulla of P7-10 rats. ⋯ Finally, in non-decerebrated pups, chemical lesions within the inhibitory area resulted in significant reductions in atonia durations, as well as decoupling of atonia from a second component of infant sleep, myoclonic twitching; specifically, twitches occasionally occurred during periods of high muscle tone, a condition reminiscent of "REM without atonia" as described in adults. In summary, we document the existence of an area within the ventromedial medulla of infant rats that (i) causes atonia when stimulated; (ii) contains units that exhibit atonia-related discharge profiles during sleep-wake cycling; and (iii) when lesioned, results in the partial loss of atonia and decoupling of the components of sleep. All together, these findings demonstrate that muscle atonia is actively regulated very early in ontogeny.
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Comparative Study
Influence of feeding status on neuronal activity in the hypothalamus during lipopolysaccharide-induced anorexia in rats.
Fasting attenuates disease-associated anorexia, but the mechanisms underlying this effect are not well understood. In the present study, we investigated the extent to which a 48 h fast alters hypothalamic neuronal activity in response to the anorectic effects of lipopolysaccharide in rats. Male rats were fed ad libitum or fasted, and were injected with i.p. saline or lipopolysaccharide (250 microg/kg). ⋯ Lipopolysaccharide-induced circulating levels of interleukin-1 were similar across feeding status. Finally, fasting, but not lipopolysaccharide, affected circulating level of leptin and appetite-related neuropeptides expression in the arcuate nucleus. Together, our data show that fasting modulates lipopolysaccharide-induced anorexia and body weight loss in association with neural changes in specific hypothalamic nuclei.
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The saphenous partial ligation (SPL) model is a new, easily performed, rodent model of neuropathic pain that consists of a unilateral partial injury to the saphenous nerve. The present study describes behavioral, pharmacological and molecular properties of this model. Starting between 3 and 5 days after surgery, depending on the modality tested, animals developed clear behaviors indicative of neuropathic pain such as cold and mechanical allodynia, and thermal and mechanical hyperalgesia compared with naive and sham animals. ⋯ Neurobiological studies looking at the expression of mu opioid receptor (MOR), cannabinoid CB(1) and CB(2) receptors showed a significant increase for all three receptors in ipsilateral paw skin, L3-L4 dorsal root ganglia and spinal cord of neuropathic rats compared with naive and sham animals. These changes in MOR, CB(1) and CB(2) receptor expression are compatible with what is observed in other neuropathic pain models and may explain the analgesia produced by morphine and WIN 55,212-2 administrations. In conclusion, we have shown that the SPL is an adequate model that will provide a new tool for clarifying peripheral mechanisms of neuropathic pain in an exclusive sensory nerve.
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We studied the neuronal basis of the motivational response to two powerful but radically different rewards-cocaine and maternal nurturing of pups in the postpartum rat (dam) which is in a unique motivational state. We used a place preference method designed to offer a choice between cues associated with a natural reinforcer (pups) and those associated with a pharmacologic reinforcer (cocaine). Using c-Fos or cocaine- and amphetamine-regulated transcript (CART) immunocytochemistry, we identified the neuronal groups that are activated when the dams expressed a preference for either cues-associated with pups or cues-associated with cocaine. ⋯ These responses were identified in the absence of the stimuli (cocaine or pups) and are proposed to be, in part, activation of these neurons related to motivational processing. Neither the distribution of neurons responding to pup-associated cue preference nor the demonstration that CART-expressing neurons are responsive to reward-associated cue preference has been previously reported. We hypothesize that the expression of preference for cocaine versus pup-associated cues is made possible by the concerted activity of these regionally distributed networks of neurons that are in part specific to the preference response.