Neuroscience research
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Neuroscience research · Jun 1996
Comparative StudyThe role of cholinergic systems in the expression of morphine withdrawal.
Both oxotremorine and physostigmine both in doses ranging from 25 to 100 micrograms/kg produced dose-dependent attenuation of withdrawal jumping and potentiation of 'wet dog' shakes, burrowing, hypothermia and body weight loss precipitated by naloxone (1 mg/kg, i.p.) in morphine-dependent mice. On the other hand, atropine sulphate (2-20 mg/kg) dose-dependently attenuated all naloxone precipitated withdrawal symptoms except withdrawal hypothermia which was further potentiated. However, the peripherally acting derivative atropine methyl nitrate (2-10 mg/kg) also attenuated all naloxone-induced withdrawal symptoms except jumping, which was not significantly modified. ⋯ Withdrawal body weight loss was dose-dependently attenuated but 'wet dog' shakes, burrowing and hypothermia were markedly potentiated by hyoscine. Our results suggest that a combination of central muscarinic activation and peripheral muscarinic blockade can partially ameliorate precipitated morphine withdrawal. Differences observed between atropine and hyoscine with regard to their modifying effects on withdrawal symptoms may be explained on the basis that the drugs may be acting on the different subpopulations of the muscarinic receptor or through non-cholinergic systems.
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Neuroscience research · Jun 1996
Comparative StudyDual effect of serotonin on formalin-induced nociception in the rat spinal cord.
To examine the role of the descending serotonergic system in the regulation of spinal nociceptive processing, the effects of serotonin (5-HT) and selective ligands for 5-HT receptor subtypes on persistent nociception were investigated. Formalin (5% formaldehyde) injected into the plantar region of the rat hindpaw induced two phases of aversive responses such as licking and biting. Intrathecal administration of selective 5-HT3 receptor antagonists, granisetron (0.1-100 pmol/rat) and ondansetron (1-1000 pmol/rat), reduced the second phase of the formalin-induced aversive responses without affecting the first one. ⋯ Intrathecal administration of 5-HT showed a dual effect on the second phase of the aversive responses in the 5,7-DHT-treated rats; 5-HT inhibited the aversive responses when administered at a low dose (0.1 nmol/rat) but facilitated them at a high dose (1 nmol/rat). In addition, the inhibitory and facilitatory effects of intrathecal 5-HT were blocked by its co-administration with NAN190, a 5-HT1A receptor antagonist, and granisetron, respectively. These results suggest that 5-HT suppresses formalin-induced nociception in the spinal cord via the 5-HT1A receptor and facilitates it via the 5-HT3 receptor.