جستجوی مقالات مرتبط با کلیدواژه « Cannabinoid » در نشریات گروه « پزشکی »

The anticonvulsant effect of cannabinoid compound has been shown in various models of seizure. On the other hand, there are controversial findings about the role of large conductance calcium-activated potassium (BK) channels in the pathogenesis of epilepsy. In this study, the effect of arachidonyl-2′-chloroethylamide (ACEA), a CB1 receptor agonist, and a BK channel antagonist, paxilline, either alone or in combination was investigated. Both pentylenetetrazole (PTZ) and maximal electroshock (MES) acute models of seizure were used to evaluate the protective effects of drugs. Mice were randomly selected in different groups: (i) control group; (ii) groups received different doses of either paxilline or ACEA; and (iii) groups received combinations of ACEA and paxillin at different doses. In MES model, prevention of hindlimb tonic extension (HLTE) was considered as protective effect. In PTZ model, the required dose of PTZ (mg/kg) to induce tonic-clonic seizure with loss of righting reflex was considered as seizure threshold. In PTZ model, while administration of ACEA per se (5 and 10 mg/kg) caused protective effect against seizure, however, co-administration of ACEA and ineffective doses of paxilline attenuated the antiseizure effects of paxilline. In MES model, while pretreatment by ACEA showed protective effects against seizure, however, co-administration of paxilline and ACEA caused an antagonistic interaction for their antiseizure properties. Our results showed a protective effect of ACEA in both PTZ and MES acute models of seizure. This effect was attenuated by co-administration with paxilline, suggesting the involvement of BK channels in antiseizure activity of ACEA.

Opioids and cannabinoids are two important compounds that have been shown to influence the activity of magnocellular neurons (MCNs) of supraoptic nucleus (SON). The interaction between opioidergic and cannabinoidergic systems in various structures of the brain and spinal cord is now well established, but not in the MCNs of SON.
In this study, whole cell patch clamp recording of neurons in rat brain slice was used to investigate the effect of acute morphine and cannabinoid administration on spontaneous inhibitory and excitatory spostsynaptic currents (sIPSCs and sEPSCs) in MCNs.
Bath application of morphine produced an increase in sEPSCs frequency and a decrease in sIPSCs frequency. In contrast, bath application of URB597 (fatty acid amide hydrolase (FAAH) inhibitor) produced a decrease in sEPSCs frequency but an increase in sIPSCs frequency. WIN55212-2 (cannabinoid receptor agonist) decreased both sIPSCs and sEPSCs frequencies of MCNs. Co-application of morphine and URB597 attenuated the effect of morphine on MCNs.
Taken together, these data indicated that at the cellular level, pharmacological augmentation of endocannabinoids could attenuate morphine effects on MCNs.

The pharmacological interaction between cannabinoidergic system and vanilloid type 1 (TRPV1) channels has been investigated in various conditions such as pain and anxiety. In some brain structure including hippocampus, CB1 and TRPV1 receptors coexist and their activation produces opposite effect on excitability of neurons. In this study, we tested the hypothesis that TRPV1 channel is involved in the modulation of cannabinoid effects on pentylenetetrazole (PTZ)-induced seizure threshold. In single therapy, male mice (n = 10 per group) received either TRPV1 receptor antagonist capsazepine, CB1 receptor agonist ACEA or anandamide reuptake inhibitor VDM11. In combination therapy, mice were treated with either capsazepine-ACEA or capsazepine-VDM11 combination prior to seizure test. Thirty min later, mice were submitted to infusion of PTZ (1%, 0.25 ml/min) into tail vein and the dose of PTZ to induce clonic convulsion was considered as seizure threshold. Administration of capsazepine and ACEA per se produced protective effects against PTZ-induced seizure, while administration of VDM11 per se did not produce such a protection effect. The anticonvulsant actions of both capsazepine and ACEA were attenuated after co-administration of these compounds. Moreover, the anticonvulsant action of capsazepine was attenuated after co-administration with VDM11. The results suggest an interaction between cannabinoidergic system and TRPV1 receptors in protection against acute PTZ-induced seizure in mice.

A large body of evidence suggests that the cannabinoid CB1 receptor plays a key role in the regulation of emotional behaviors. The present study was designed to evaluate the effects of CB1 agonist and antagonist on anxiety-like behaviors in the lateral septum (LS) region of the rat brain using elevated plus maze test. Rats were anesthetized with ketamine and xylazine and special cannulas were inserted stereotaxically into the LS region. After 1 week of recovery, the effects of intra-LS administration of the CB1 receptor agonist, WIN 55,212-2 and CB1 receptor antagonist, AM251, on %OAT and %OAE were measured. Moreover, the effects of pretreatment with AM251 on the response induced by intra-LS administration of WIN 55,212-2 were also assessed. Intra-LS administration of WIN 55,212-2 (0.001, 0.005 and 0.5μg/rat) decreased the %OAT and %OAE but not locomotor activity, showing an anxiogenic-like response. Intra-LS injection of different doses of AM251 (0.001, 0.01 and 0.1 µg/rat) did not significantly alter the anxiety-like parameters on the plus-maze test. However, intra-LS injections of AM251 (0.01 µg/rat) significantly reversed WIN 55,212-2-induced anxiogenic-like effects. The results suggest that the cannabinoid system of the lateral septum modulates anxiety-like behavior through CB1 receptor.

Orexinergic projection originated from the lateral hypothalamus (LH) to the ventral tegmental area (VTA) has an important role in the acquisition of drug conditioned place preference (CPP). In the present study, we tried to evaluate the effect of LH stimulation on conditioned place preference paradigm and role of CB1 receptors located in the VTA in development of reward-related behaviors in rats. One hundred twenty adult male Wistar rats weighing 220-330 g were unilaterally implanted by two separate cannulae into the LH and VTA. The CPP paradigm was done. Our findings showed that unilateral intra-LH administration of carbachol (62.5, 125 and 250 nmol/0.5 µl saline), during conditioning phase, induced CPP in a dose-dependent manner. Additionally, intra-VTA administration of AM251 (5, 25 and 125 nmol/0.3 µl DMSO) as a CB1 receptor antagonist, just 5 min before carbachol during the 3-day conditioning phase, could dose dependently inhibit the development of LH stimulation-induced CPP in the rats. It is supposed that the projection from LH to VTA is involved in LH chemical stimulation-induced CPP and CB1 receptor in the VTA has a modulatory role in this phenomenon.