Pharmacology, biochemistry, and behavior
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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
The partial 5-HT(1A) agonist buspirone reduces the expression and development of l-DOPA-induced dyskinesia in rats and improves l-DOPA efficacy.
Dopamine (DA) replacement therapy with l-DOPA remains the standard pharmacotherapy for Parkinson's disease (PD). Unfortunately, chronic l-DOPA treatment is accompanied by development of motor fluctuations and l-DOPA-induced dyskinesia (LID). While serotonin (5-HT)(1A) agonists acutely reduce these complications, their prophylactic and long-term effects are not well-delineated. ⋯ AIMs and FAS were measured throughout. In l-DOPA-primed rats, buspirone dose-dependently reduced LID and improved l-DOPA-related motor performance due to action at the 5-HT(1A) receptor. In l-DOPA-naïve rats, buspirone delayed LID development while improving l-DOPA's anti-parkinsonian efficacy indicating the potential long-term benefits of 5-HT(1A) agonists for reduction of l-DOPA-related side effects.
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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.
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Treatment of postpartum female rats with morphine inhibits maternal behavior. The same type of treatment stimulates foraging in adult animals. The aim of the present study was to investigate, in lactating rats, the functional role of opioid systems in the choice between caring for pups versus hunting insects. ⋯ Consistently, naloxone treatment induced a decrease in number of insects captured and an increase in the percentage of animals displaying nursing behavior. These results provide important insight into the role of opioidergic transmission in the regulation of behavioral selection during lactation. The present results suggest that endogenous opioids may stimulate hunting by replacing maternal behavior during lactation.
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Pharmacol. Biochem. Behav. · Aug 2007
Evaluation of pain behavior and bone destruction in two arthritic models in guinea pig and rat.
The primary aim of the study was to describe and correlate pain behavior and changes in bone morphology in animal models of arthritis both in rats and guinea pigs. Either complete Freund's adjuvant (CFA) or mono-iodoacetate (MIA) solution was injected into the left knee joint to obtain a model for rheumatoid arthritis and osteoarthritis, respectively. Subsequently, animals were behaviorally tested during a period of 12 days after CFA injection and at least 19 days after MIA injection. ⋯ To evaluate bone destruction mu-computed tomography scans of the arthritic knee were taken on the last experimental day. Different bone parameters indicative of osteolysis and decreased trabecular connectivity were significantly correlated with the observed pain behavior. Detailed description of morphological changes in arthritic joints better characterizes the different animal models and might add to the knowledge on the working mechanisms of analgesic compounds that have an influence on bone structures in arthritis.