Pharmacology, biochemistry, and behavior
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Pharmacol. Biochem. Behav. · Oct 2011
Comparative StudyMorphine sensitization as a model of mania: comparative study of the effects of repeated lithium or carbamazepine administration.
Repeated unavoidable stress induces in rats decreased reactivity to avoidable stressors and an anhedonia-like condition that are reverted by long-term antidepressant treatments and regarded as models of core symptoms of depression. Morphine-sensitized rats present resilience to stress-induced behavioral deficits and, if hyporeactivity to stress models a depressive symptom, stress resistance can be regarded as a manic symptom. This hypothesis is supported by the observation that long-term lithium administration reinstates sensitivity to stress in sensitized rats. ⋯ In sensitized rats, neither carbamazepine nor lithium administration interfered with the dopaminergic response to VS and the acquisition of VAB. In summary, the effect of carbamazepine on the stress resilience of sensitized rats further supported the hypothesis that morphine sensitization might model some symptoms of mania. Moreover, in control rats carbamazepine treatment elicited an anhedonia-like condition that clearly distinguished the effects of this drug from those of lithium.
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Pharmacol. Biochem. Behav. · Oct 2011
Fatty acid amide hydrolase blockade attenuates the development of collagen-induced arthritis and related thermal hyperalgesia in mice.
Fatty acid amide hydrolase (FAAH) is the primary degradative enzyme of the endocannabinoid anandamide (N-arachidonoylethanolamine), which activates cannabinoid CB(1) and CB(2) receptors. FAAH disruption reduces nociception in a variety of acute rodent models of inflammatory pain. The present study investigated whether these actions extend to the chronic, collagen-induced arthritis (CIA) model. ⋯ Similarly, repeated administration of the FAAH inhibitor URB597 reduced CIA severity, and acute administration of rimonabant, but not SR144528, blocked the anti-hyperalgesic effects of prolonged FAAH inhibition, suggesting that prolonged CB(2) receptor activation reduces the severity of CIA, whereas acute CB(1) receptor activation reduces CIA-induced hyperalgesia. In contrast, acute administration of URB597 elicited a CB(1) receptor-dependent anti-hyperalgesic effect. The observed anti-arthritic and anti-hyperalgesic properties of FAAH inhibition, coupled with a lack of apparent behavioral alterations, suggest that endocannabinoid modulating enzymes offer a promising therapeutic target for the development of novel pharmacological approaches to treat rheumatoid arthritis and associated hyperalgesia.
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Pharmacol. Biochem. Behav. · Oct 2011
The antinociceptive potency of N-arachidonoyl-dopamine (NADA) and its interaction with endomorphin-1 at the spinal level.
The endogenous N-arachidonoyl-dopamine (NADA) activates both transient receptor potential vanilloid1 (TRPV1) and cannabinoid-1 (CB(1)) receptors. The goal of this study was to characterize the antinociceptive potential of NADA on inflammatory thermal hyperalgesia in rats at spinal level, and to determine its interaction with endomorphin-1 (EM) at the spinal level. The effects of NADA and EM on thermal hyperalgesia were evaluated in rats with a unilateral hind paw carrageenan-induced inflammation. ⋯ The antihyperalgesia caused by 15 μg NADA was inhibited by the TRPV1 antagonist AMG9810, but not by CB(1) antagonist/inverse agonist AM 251, whereas the effect of 50 μg NADA was decreased by both drugs. Co-administration of EM with NADA in 1:15 and 1:50 ratios produced a short-lasting potentiation, but isobolographic analysis for the whole investigated period revealed additive interaction between the two endogenous ligands. The results show that both TRPV1 and CB(1) receptor activation play a substantial role in the antinociceptive effects of NADA at spinal level, while co-administration of NADA with EM did not show potentiation.
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Pharmacol. Biochem. Behav. · Oct 2011
Blockade of 5-HT7 receptors reduces tactile allodynia in the rat.
This study assessed the role of systemic and spinal 5-HT(7) receptors on rats submitted to spinal nerve injury. In addition, the 5-HT(7) receptors level in dorsal root ganglion and spinal cord was also determined. Tactile allodynia was induced by L5/L6 spinal nerve ligation. ⋯ Data suggest that spinal 5-HT(7) receptors play a pronociceptive role in neuropathic rats. Results also indicate that spinal nerve injury leads to a reduced 5-HT(7) receptors level in pain processing-related areas which may result from its nociceptive role in this model. Data suggest that selective 5-HT(7) receptor antagonists may function as analgesics in nerve injury pain states.
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Pharmacol. Biochem. Behav. · Oct 2011
Synergistic anti-allodynic effects of nociceptin/orphanin FQ and cannabinoid systems in neuropathic mice.
Combinations of analgesics from different classes are commonly used in the management of chronic pain. The goal is to enhance pain relief together with the reduction of side effects. The present study was undertaken to examine the anti-allodynic synergy resulting from the combination of WIN 55,212-2, a cannabinoid CB1 receptor agonist, and JTC-801, a nociceptin/orphanin FQ receptor antagonist, on neuropathic pain. ⋯ Both WIN 55,212-2 and JTC-801 produced dose-dependent mechanical and cold anti-allodynic effects. As shown by isobolographic analysis, WIN 55,212-2/JTC-801 combinations interacted synergistically at all three ratios studied in the mechanical allodynia assay. In conclusion, co-administration of a cannabinoid with a nociceptin/orphanin FQ receptor antagonist resulted in a synergistic interaction, which may have utility in the pharmacological treatment of neuropathic pain.