Behavioural pharmacology
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Behavioural pharmacology · Feb 2008
Pharmacologic investigation of the mechanism underlying cold allodynia using a new cold plate procedure in rats with chronic constriction injuries.
Cold allodynia is a frequent clinical symptom of patients with neuropathic pain. Despite numerous studies of cold allodynia, using animal models of neuropathic pain, little is known about its underlying mechanisms. This study was performed to establish a method for the pharmacologic evaluation of cold allodynia using several analgesics in a chronic constriction injury (CCI) rat model of neuropathic pain. ⋯ Under this condition, both the sodium channel blocker mexiletine (10 and 30 mg/kg, subcutaneously) and the calcium channel alpha2delta subunit blocker pregabalin (30 and 100 mg/kg, orally) significantly suppressed cold allodynia. Additionally, both resiniferatoxin (0.3 mg/kg, subcutaneously), an ultrapotent analog of capsaicin that desensitizes C fibers, and the VR1 channel antagonist N-(4-tertiarybutylphenyl)-4-(3-chloropyridin-2-yl) tetrahydropyrazine-1(2H)-carboxamide (10 and 30 mg/kg, orally) significantly prolonged the paw withdrawal latency. In conclusion, our data suggest that the activation of C fibers mediates cold allodynia.
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Behavioural pharmacology · Nov 2007
Effects of AM1346, a high-affinity CB1 receptor selective anandamide analog, on open-field behavior in rats.
AM1346 is a cannabinoid receptor type 1 (CB1R) anandamide analog [alkoxyacid amide of N-eicosa-(5Z, 8Z, 11Z, 14Z)-tetraenylamine] with high affinity and selectivity for the CB1 vs. CB2 receptor [Ki (CB1)=1.5 nmol/l; Ki (CB2)=152 nmol/l]. The present study characterized the effects of AM1346 (5.6-18 mg/kg) and its interaction with the CB1R antagonist/inverse agonist SR141716 (1-5.6 mg/kg) on open-field behaviors of rats. ⋯ The present profile of behavioral effects for AM1346 is consistent with its designation as a CB1R agonist. When combined with drug discrimination data (surmountable antagonism of effects of SR141716 by Delta(9)-THC and AM1346 but not by methanandamide, i.e. AM356), these data indicate that the anandamide analog AM1346 may be more behaviorally similar to cannabinoids like Delta(9)-THC than to other anandamide-based molecules such as methanandamide.
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Behavioural pharmacology · Nov 2007
Chronic forced swim stress inhibits ultra-low dose morphine-induced hyperalgesia in rats.
Ultra-low doses of morphine (UL-morphine) induce hyperalgesia, which is assumed to be mediated by stimulatory G proteins (G(alphas)) signaling pathway. G(alphas) pathway inhibition and chronic stress both attenuate development of tolerance to analgesic effect of morphine. This study evaluated the effect of chronic stress on UL-morphine-induced hyperalgesia to find out if chronic stress interacts with the G(alphas) signaling pathway. ⋯ Inhibition of UL-morphine hyperalgesia by chronic stress suggests that chronic stress interacts with the G(alphas) signaling pathway, which is responsible for UL-morphine-induced hyperalgesia. The absence of this effect in the ADX-rats or after repetitive dexamethasone administration demonstrates that hypothalamic-pituitary-adrenal (HPA) axis activation is necessary for controlling UL-morphine-induced hyperalgesia. Finally, the interaction of stress with the G(alphas) signaling pathway may provide an explanation for the inhibitory effect of stress on development of tolerance to the analgesic effect of morphine.
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Behavioural pharmacology · May 2007
Morphine-induced antinociception in the formalin test: sensitization and interactions with D1 and D2 dopamine receptors and nitric oxide agents.
In this study, the effects of dopamine receptor antagonists and nitric oxide agents on morphine-induced sensitization in the formalin test in mice have been investigated. Repeated daily intraperitoneal administration of morphine (30 mg/kg for 3 days) followed by a 11-day wash out period increased morphine-induced antinociception in the formalin test, which may be due to sensitization. The antinociceptive response to higher doses of morphine (6 and 9 mg/kg) but not 3 mg/kg was significantly increased in sensitized animals compared with control groups. ⋯ In the second part of the study, the animals received SCH23390 (D1 receptor antagonist), sulpiride (D2 receptor antagonist), L-Arg (nitric oxide precursor) and NG-nitro-L-Arg methylester (nitric oxide synthase inhibitor) during repeated morphine administration, to evaluate the role of dopamine receptor antagonists and nitric oxide agents in this phenomenon. Pretreatment of animals with NG-nitro-L-Arg methylester (20 mg/kg) and sulpiride (100 mg/kg) during morphine sensitization decreased the antinociceptive response to higher doses of morphine in the formalin test. It is concluded that D2 dopamine receptor and nitric oxide mechanisms may be involved at least partly in morphine-induced sensitization in the formalin test.
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Behavioural pharmacology · Feb 2007
Controlled Clinical TrialGabapentin does not reduce smoked cocaine self-administration: employment of a novel self-administration procedure.
Previously, we reported that gabapentin, a nonselective gamma-aminobutyric acid agonist, reduced 'positive' subjective effects of cocaine without reducing cocaine self-administration. We speculated that the self-administration procedure used in that study was not sensitive to subtle shifts in the reinforcing effects of cocaine. Thus, this study examined the effects of gabapentin maintenance on cocaine self-administration using a purchase-cocaine choice procedure. ⋯ Choice to self-administer cocaine increased significantly with escalating cocaine doses; gabapentin maintenance did not alter choice to self-administer cocaine. These results concur with findings from our previous investigations of gabapentin and with those from a clinical trial examining the effects of larger gabapentin doses on cocaine use by treatment-seeking cocaine-dependent individuals. Together, the data indicate that gabapentin does not show promise as a treatment medication for cocaine dependence.