Pharmacology, biochemistry, and behavior
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Pharmacol. Biochem. Behav. · Jan 2013
The long-lasting sensitization of primary afferent nociceptors induced by inflammation involves prostanoid and dopaminergic systems in mice.
In recent years, evidence that sensitization of primary afferent nociceptors is an important event associated with chronic pain has been accumulating. The present study aimed to evaluate the participation of the prostaglandin and sympathetic components in the long-lasting sensitization of nociceptors induced by acute inflammation in mice. The intraplantar administration of carrageenan (100 μg) enhanced the nociceptive response to a small dose of PGE(2) (9 ng/paw) or dopamine (3 μg/paw) up to 30 days later. ⋯ In agreement with this idea, the previous intraplantar administration of hyperalgesic doses of PGE(2) or dopamine also induced long-lasting sensitization, which was fully prevented by pretreatment with EP(4) and D(1) antagonists, respectively. In summary, the present work described in mice a long-lasting sensitization of nociceptors, initiated by an acute inflammatory stimulation and dependent on dopaminergic and prostanoid systems. The present data represent new insights on the mechanisms of peripheral sensitization that could contribute to establish the basis of new therapeutic strategies for acute and chronic inflammatory pain.
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Pharmacol. Biochem. Behav. · Dec 2012
The role of the NMDA receptors and l-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of duloxetine in the forced swimming test.
Duloxetine is a selective serotonin and noradrenaline reuptake inhibitor used as antidepressant. However, its mechanisms of action are not fully understood. This study investigated the effect of duloxetine in the mouse forced swimming test (FST) and in the tail suspension test (TST) and the involvement of the NMDA receptors and the l-arginine-NO-cGMP pathway in its effect in the FST. ⋯ Moreover, the administration of duloxetine (10mg/kg) produced a reduction in NOx levels in the hippocampus and cerebral cortex. Altogether the results suggest that the effect of duloxetine in the FST is dependent on either a blockade of NMDA receptors or an inhibition of NO. In addition, our results further reinforce the role of NMDA receptors and l-arginine-NO-cGMP pathway, besides the monoaminergic systems, in the mechanism of action of current prescribed antidepressant agents.
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Pharmacol. Biochem. Behav. · Dec 2012
Fingolimod (FTY720) inhibits neuroinflammation and attenuates spontaneous convulsions in lithium-pilocarpine induced status epilepticus in rat model.
Accumulating evidence has shown that neuroinflammation plays a key role in epileptogenesis. However, the efficacy of anti-inflammatory agents for preventing epilepsy remains controversial. Fingolimod (FTY720), a sphingosine-1-phosphate (S1P) analog, has potent anti-inflammatory effects in multiple sclerosis (MS) patients and animal models. ⋯ During 21-34days post-SE, the incidence, duration, frequency and severity of SCs significantly decreased in FTY720 treated rats compared with saline treated rats. Aberrant MFS was also attenuated by FTY720 administration. These results suggest that FTY720 exerts anti-inflammatory and antiepileptogenic effects in lithium-pilocarpine model of epilepsy and it may provide a new therapeutic approach for prevention of epileptogenesis.
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Pharmacol. Biochem. Behav. · Nov 2012
Double-dissociation of D1 and opioid receptor antagonism effects on the acquisition of sucrose-conditioned flavor preferences in BALB/c and SWR mice.
Sugar appetite is influenced by unlearned attractions to sweet taste and learned responses to sugars' taste and post-ingestive actions. In rats, sugar-conditioned flavor preferences (CFP) are attenuated by dopamine D1 (SCH23390: SCH), but not by opioid (naltrexone: NTX), receptor antagonism. Sucrose-CFP occurs in BALB/c and SWR inbred mice that differ in their suppressive effects of SCH and NTX on sucrose intake. ⋯ In the initial two-bottle test, sucrose-CFP acquisition was significantly reduced in BALB NTX (54%), but not in BALB SCH (77%) groups relative to the BALB Veh group (85%). In contrast, sucrose-CFP acquisition was significantly reduced in SWR SCH (61%), but not in SWR NTX (83%) groups relative to the SWR Veh group (86%). DA D1 and opioid receptor signaling modulate acquisition and/or expression of sucrose-CFP in mice with significant strain differences observed.
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Pharmacol. Biochem. Behav. · Nov 2012
Antinociceptive effects of tramadol in co-administration with metamizol after single and repeated administrations in rats.
Combinations of two analgesic drugs of the same or different class are widely used in clinical therapy to enhance its antinociceptive effects and reduce the side effects. In order to evaluate a possible antinociceptive synergistic interaction of metamizol s.c., a nonsteroidal antiinflammatory drug (NSAID), and tramadol s.c., an atypical opioid (opioid receptor agonist), were administered alone or in combination. In the present study, the antinociceptive efficacy and the possible development of pharmacological tolerance produced by the combination tramadol plus metamizol during a 4-day treatment in rats using the plantar test was evaluated. ⋯ The antinociceptive efficacy of tramadol and metamizol co-administration gradually decreased after the second injection. These data suggest that when the combination is given in a unique administration it results in an important potentiation of their individual antinociceptive effects. But, the repeated coadministration of tramadol plus metamizol results in a development of tolerance.