Pharmacology, biochemistry, and behavior
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Pharmacol. Biochem. Behav. · Nov 2007
Analysis of the antinociceptive effect of systemic administration of tramadol and dexmedetomidine combination on rat models of acute and neuropathic pain.
The aim of the present study was to investigate the possible antinociceptive effect of systemic administration of tramadol and dexmedetomidine either alone or in combination on acute and neuropathic pain models in rats. The antinociceptive effects of intraperitoneal (i.p.) tramadol (5-20 mg/kg) and dexmedetomidine (5-20 microg/kg) and three different combinations of tramadol+dexmedetomidine (5+5, 5+10 and 10+5, mg/kg+microg/kg, respectively) were measured by tail-flick and hot-plate methods in acute pain. The effects on the sciatic nerve ligation-induced neuropathic pain was tested by i.p. administration of tramadol (5 mg/kg), dexmedetomidine (5 microg/kg) and tramadol+dexmedetomidine combination (5+5) using a thermal plantar test. ⋯ In the neuropathic pain, the antinociceptive effect exerted by tramadol+dexmedetomidine combination (5+5) was also significantly greater than their applications alone. In rotarod test, tramadol (30 and 40 mg/kg), dexmedetomidine (30 and 40 microg/kg), tramadol+dexmedetomidine combination (10+10, 20+20) produced sedation/motor-incoordination, whereas tramadol (5-20 mg/kg), dexmedetomidine (5-20 microg/kg) and tramadol+dexmedetomidine combination (5+5, 5+10 and 10+5) did not produce any effect on sedation/motor-incoordination. The combination of tramadol and dexmedetomidine was more effective in increasing the pain threshold in acute and neuropathic pain when compared with the administration of either of these drugs alone.
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Pharmacol. Biochem. Behav. · Nov 2007
Activation of peripheral and spinal histamine H3 receptors inhibits formalin-induced inflammation and nociception, respectively.
Pharmacological activation of histamine H3 receptors is known to reduce the release of inflammatory peptides, thereby reducing pain and inflammation, but the site(s) and mechanism(s) of these effects are currently unknown. The present study addressed these questions by examining the effects of the H3 agonist immepip and the H3 antagonist thioperamide on nociceptive behaviors and swelling produced during the rat formalin test. Systemic administration of immepip (5 and 30 mg/kg, s.c.) significantly attenuated formalin-induced flinching but not licking responses during both phases. ⋯ Also consistent with this pattern, intrathecal immepip (50 microg) reduced flinching responses, but had no effect on formalin-induced paw swelling. The present findings suggest that activation of H3 receptors located on peripheral and spinal terminals of deep dermal fibers attenuates formalin-induced swelling and flinching, respectively. Pharmacological stimulation of H3 receptors could be an important therapeutic approach for many disorders related to deep dermal or inflammatory pain.
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Although psilocybin has been trained in the rat as a discriminative stimulus, little is known of the pharmacological receptors essential for stimulus control. In the present investigation rats were trained with psilocybin and tests were then conducted employing a series of other hallucinogens and presumed antagonists. An intermediate degree of antagonism of psilocybin was observed following treatment with the 5-HT(2A) receptor antagonist, M100907. ⋯ LSD and MDMA partially generalized to psilocybin and these effects were completely blocked by M-100907; no generalization of PCP to psilocybin was seen. The present data suggest that psilocybin induces a compound stimulus in which activity at the 5-HT(2A) receptor plays a prominent but incomplete role. In addition, psilocybin differs from closely related hallucinogens such as 5-MeO-DMT in that agonism at 5-HT(1A) receptors appears to play no role in psilocybin-induced stimulus control.
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Pharmacol. Biochem. Behav. · Aug 2007
Co-administration of rofecoxib and tramadol results in additive or sub-additive interaction during arthritic nociception in rat.
Over the decades, nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids are the most commonly used analgesics in the management of acute and chronic pain. In order to assess a possible antinociceptive interactions, the antinociceptive effects of rofecoxib p.o., a preferential inhibitor of cyclooxygenase-2, and tramadol-hydrochloride p.o., an atypical opioid analgesic, administered either separately or in combination, were determined using a rat model of arthritic pain. The data were interpreted using the surface of synergistic interaction (SSI) analysis and an isobolographic analysis to establish the nature of the interaction. ⋯ Three combination of rofecoxib+tramadol (10.0+5.6, 10.0+10.0, and 17.8+5.6 mg/kg respectively) presented high sub-additive interactions (P<0.002: Q=9.5). The combination rofecoxib (17.8 mg/kg)+tramadol (10.0 mg/kg) caused gastric injuries less severe than those observed with indomethacin, but more severe than those obtained with rofecoxib or tramadol in single administration. The antinociceptive interaction of rofecoxib and tramadol suggests that combinations with these drugs may have no clinical utility in pain therapy.
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Pharmacol. Biochem. Behav. · Aug 2007
D-Cycloserine enhances conditioned taste aversion learning in rats.
Conditioned taste aversion (CTA) is a form of associative learning in which the pairing of a taste with a toxin causes an animal to avoid the taste. NMDA receptor mediated neurotransmission has been implicated in CTA, but the role of the NMDA receptor glycine-binding site has not been examined. To examine the effects on CTA of the glycinergic NMDA receptor agonist D-cycloserine, rats received D-cycloserine (15 mg/kg, i.p.) or vehicle 15 min before 10-min access to 0.125% saccharin, followed by a low dose of LiCl (19 mg/kg, i.p.). ⋯ Second, pretreatment with D-cycloserine did not increase the duration of "lying-on-belly" behavior induced by LiCl. Third, pretreatment with D-cycloserine did not increase c-Fos induction by either LiCl or vehicle injection in central visceral relays (the nucleus of the solitary tract, the parabrachial nucleus, the central nucleus of the amygdala, the supraoptic nucleus, and the paraventricular nucleus). These results confirm the participation of NMDA receptor, and specifically the glycine-binding site of NMDA receptor, in CTA learning.