Pharmacology, biochemistry, and behavior
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Pharmacol. Biochem. Behav. · Dec 2002
Dextromethorphan and ketamine potentiate the antinociceptive effects of mu- but not delta- or kappa-opioid agonists in a mouse model of acute pain.
Animal and clinical studies have reported potentiation of opioid antinociception by NMDA receptor antagonists such as ketamine and dextromethorphan. The aim of this study was to compare these clinically available NMDA antagonists in combination with classical morphine, mu-selective fentanyl-like opioids, the delta-opioid agonist SNC80 and the kappa-opioid agonist U50,488H. Using a mouse hot-plate test, dose-response relationships were first determined for all compounds individually and then for opioids co-administered with fixed doses of ketamine or dextromethorphan. ⋯ Dextromethorphan produced lower ED(50) values for morphine, fentanyl and sufentanil but exerted no effect on the potency of SNC80 or U50,488H. Similarly, ketamine potentiated the antinociceptive potency of morphine, fentanyl and sufentanil but not SNC80 or U50,488H. In summary, these results support the use of mu-opioid agonists in combination with NMDA antagonists, but suggest that there may be no advantage in combining dextromethorphan or ketamine with delta- or kappa-opioids in the management of acute pain.
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Pharmacol. Biochem. Behav. · Sep 2002
Antisense oligonucleotide knockdown of mGluR1 alleviates hyperalgesia and allodynia associated with chronic inflammation.
Chronic inflammation induced by injection of complete Freund's adjuvant (CFA) into one hindpaw elicits thermal hyperalgesia and mechanical allodynia in the injected paw. Metabotropic glutamate receptors (mGluRs) have been implicated in dorsal horn neuronal nociceptive responses and pain associated with short-term inflammation. The goal of the present study was to assess the role of mGluR1 in the hyperalgesia and allodynia associated with the CFA model of chronic inflammation. ⋯ When intrathecal infusion of mGluR1 AS oligonucleotide (50 microg/day) began prior to CFA injection, mechanical allodynia was attenuated from Days 1 to 8 following CFA injection, whereas heat hyperalgesia was attenuated on Day 1 and then from Days 4 to 8. When intrathecal infusion of mGluR1 AS oligonucleotide was begun 2 days after CFA injection, both mechanical allodynia and heat hyperalgesia were attenuated at all time points following the oligonucleotide infusion. Thus, the present data suggest a role for mGluR1 in persistent inflammatory nociception.
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Pharmacol. Biochem. Behav. · Jan 2002
Comparative StudyEvaluation of the anxiolytic-like effects of Cecropia glazioui Sneth in mice.
Cecropia glazioui Sneth has been used in most Latin American countries as an antihypertensive, cardiotonic, and antiasthmatic folk medicine. In the cardiovascular studies to define its antihypertensive action it was noteworthy that animals treated with the aqueous extract (AE) of C. glazioui were much calmer than control animals. That observation prompted the present study, aimed at an investigation of the effects of AE and of two semipurified fractions on mouse behavior as evaluated in the elevated plus-maze test (EPM). ⋯ A similar profile of action was observed after treatment with the butanolic fraction (Fbut) but not with the aqueous fraction (Faq). These findings suggest that the AE of C. glazioui promotes an anxiolytic-like effect in mice. The active principles responsible for this action are present in the less polar fraction of the extract, the main constituents of which are flavonoids and terpenes, among other compounds.
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Pharmacol. Biochem. Behav. · Jan 2002
Comparative StudyProlonged effect of an anesthetic dose of ketamine on behavioral despair.
The present study investigated the effect of a single, anesthetic dose of ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, on behavioral despair, an animal model of depression. Separate groups of male Wistar rats injected with an anesthetic dose of ketamine (160 mg/kg ip) and tested 3, 7, or 10 days later showed significantly less immobility in the second of two forced-swim tests compared to saline-injected controls. Ketamine- and saline-treated animals did not differ significantly in the swim tests with respect to other behavioral measures, namely diving, jumping, and head shakes. The present findings point to an ameliorative effect of ketamine on behavioral despair and support the view that NMDA antagonists may have a beneficial effect on depression.
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Pharmacol. Biochem. Behav. · Dec 2000
Enhanced locomotor stimulation by NMDA receptor antagonists in alcohol-sensitive ANT rats.
The ability of the antagonists for the N-methyl-D-aspartate (NMDA) type of glutamate receptor to modulate locomotor activity were compared in alcohol-sensitive (or alcohol-nontolerant, ANT) and alcohol-insensitive (or alcohol-tolerant, AT) rat lines. Both rat lines showed altered locomotor activity after acute injections of a competitive antagonist (LY235959), a glycine-site antagonist (L-701,324), or noncompetitive antagonists [MK-801, phencyclidine (PCP), and ketamine] of the NMDA receptor. MK-801 at 0.5 mg/kg caused a strong increase in horizontal activity in both rat lines, the effect being significantly greater in the ANT rats. ⋯ Fos immunoreactive cells in these brain regions after MK-801 treatment were more numerous in ANT than AT rats, although c-fos induction in the inferior olivary nucleus was similar in all animals after MK-801. The ANT rats showed greater locomotor stimulation also after ketamine and LY235959, while stimulation induced by PCP and depression induced by L-701,324 did not differ between the rat lines. The data suggest that altered NMDA receptor-mediated processes may correlate with differences in innate alcohol sensitivity in the ANT/AT rat model.