Behavioural pharmacology
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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.