Pharmacology, biochemistry, and behavior
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Pharmacol. Biochem. Behav. · Sep 2014
The microinjection of a cannabinoid agonist into the accumbens shell induces anxiogenesis in the elevated plus-maze.
This study investigated the effect of a cannabinoid agonist injected into the shell region of the nucleus accumbens (nAcb shell) on anxiety-related behaviors. The animals (male Wistar rats) were unilaterally microinjected with either ACEA (arachidonyl-2'-chloroethylamide a CB1 receptor agonist) at doses of 0.005, 0.05 or 0.5 pmol, or vehicle (ethanol 0.04% in saline 0.9%) and submitted to the elevated plus-maze (EPM), a pre-clinical test of anxiety. ⋯ The locomotor activity was not changed at the dose of 0.05 pmol ACEA microinjected into the nAcb shell. The present data suggest that activation of cannabinoid receptors in the nAcb shell may modulate fear/anxiety in the EPM.
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Pharmacol. Biochem. Behav. · Sep 2014
Interaction between the dopaminergic and opioidergic systems in dorsal hippocampus in modulation of formalin-induced orofacial pain in rats.
The hippocampus is a region of the brain that serves several functions. The dopaminergic system acts through D1- and D2-like receptors to interfere in pain modulation and the opioid receptors play major roles in analgesic processes and there are obvious overlaps between these two systems. The present study investigated the interaction between the opioidergic and dopaminergic systems in the dorsal hippocampus (CA1) region for formalin-induced orofacial pain. ⋯ Sulpiride reversed the antinociceptive effects of morphine only in the first phase, but this result was not significant. Our findings suggest that there is cross-talk between the opioidergic and dopaminergic systems. Opioidergic neurons also exerted antinociceptive effects by modulation of the dopaminergic system in the CA1 region of the brain.
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Pharmacol. Biochem. Behav. · Sep 2014
Combined inhibition of FAAH and COX produces enhanced anti-allodynic effects in mouse neuropathic and inflammatory pain models.
Common pharmacological treatments of neuropathic and chronic inflammatory pain conditions generally lack efficacy and/or are associated with significant untoward side effects. However, recent preclinical data indicate that combined inhibition of cyclooxygenase (COX) and fatty acid amide hydrolase (FAAH), the primary catabolic enzyme of the endocannabinoid N-arachidonoylethanolamine (anandamide; AEA), produces enhanced antinociceptive effects in a variety of murine models of pain. Accordingly, the primary objective of the present study was to investigate the consequences of co-administration of the COX inhibitor diclofenac and the highly selective FAAH inhibitor PF-3845 in models of neuropathic pain (i.e., chronic constrictive injury of the sciatic nerve (CCI)) and inflammatory pain induced by an intraplantar injection of carrageenan. Here, we report that combined administration of subthreshold doses of these drugs produced enhanced antinociceptive effects in CCI and carrageenan pain models, the latter of which was demonstrated to require both CB1 and CB2 receptors. The combined administration of subthreshold doses of these drugs also increased AEA levels and decreased prostaglandin levels in whole brain. Together, these data add to the growing research that dual blockade of FAAH and COX represents a potential therapeutic strategy for the treatment of neuropathic and inflammatory pain states. ⋯ Tandem inhibition of FAAH and COX attenuates inflammatory and neuropathic pain states, which may avoid potentially harmful side effects of other therapeutic options, such as NSAIDs or opioids.
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Pharmacol. Biochem. Behav. · Sep 2014
In vivo effects of synthetic cannabinoids JWH-018 and JWH-073 and phytocannabinoid Δ9-THC in mice: inhalation versus intraperitoneal injection.
Human users of synthetic cannabinoids (SCBs) JWH-018 and JWH-073 typically smoke these drugs, but preclinical studies usually rely on injection for drug delivery. We used the cannabinoid tetrad and drug discrimination to compare in vivo effects of inhaled drugs with injected doses of these two SCBs, as well as with the phytocannabinoid Δ(9)-tetrahydrocannabinol (Δ(9)-THC). Mice inhaled various doses of Δ(9)-THC, JWH-018 or JWH-073, or were injected intraperitoneally (IP) with these same compounds. ⋯ Injected JWH-018 and JWH-073 fully substituted for Δ(9)-THC, but substitution was partial (JWH-073) or required relatively higher doses (JWH-018) when drugs were inhaled. These studies demonstrate that the SCBs JWH-018 and JWH-073 elicit dose-dependent, CB1 receptor-mediated Δ(9)-THC-like effects in mice when delivered via inhalation or via injection. Across these routes of administration, differences in cataleptic effects and, perhaps, discriminative stimulus effects, may implicate the involvement of active metabolites of these compounds.
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Pharmacol. Biochem. Behav. · Sep 2014
Antinociceptive effects of systemic tanshinone IIA on visceral and somatic persistent nociception and pain hypersensitivity in rats.
Previous studies showed that tanshinone IIA (TIIA), an important lipophilic component of Danshen, has been well-established to exhibit various neuroprotective actions in the nervous system. Although we previously reported that TIIA had a significant anti-nociceptive effect in complete Freund's adjuvant (CFA)-induced pain, it is surprisingly noted that few pharmacological studies have been carried out to explore the possible analgesic action of TIIA in animals and the appropriate indications for treatment of clinical pain remain unclear. Therefore, in the present study, by using both somatic and visceral pain models, the antinociceptive and antihyperalgesic effects of TIIA were evaluated by intraperitoneal administration in rats. ⋯ Moreover, in the formalin test, the antinociception of TIIA was significant for both phases 1 and 2 in the pretreatment groups, but only effective for phase 2 in the post-treatment group. In the acetic acid writhing test, the number of writhes was effectively blocked by both pre- and post-treatment of TIIA. Taken together, these results provide a new line of evidence showing that TIIA is also able to produce analgesia against various 'phenotypes' of nociception and hypersensitivity.