Synthesis and anticonvulsant activity of novel 2-amino-5-[4-chloro-2-[2-chlorophenoxy] phenyl] -1, 3, 4-thiadiazole derivatives

Several novel 2-amino-5-[4-chloro-2-[2-chlorophenoxy]phenyl]-1, 3, 4-thiadiazole derivatives 4a-d were synthesized and their anticonvulsant activity was determined by evaluation of the ability of theses compounds to protect mice against convulsion induced by a lethal doses of pentylentetrazole [PTZ] and maximal electroshock [MES]. The result of anticonvulsant data shows that among the synthesized compounds, 5-[4-chloro-2-[2-chlorophenoxy]phenyl]-N-ethyl-1, 3, 4-thiadiazol-2-amine 4c was the most active compound in both MES and PTZ tests with an ED[50] of 20.11 and 35.33 mg/kg, respectively

[Effect of the dorsal raphe nucleus electrical stimulation on evoked response of the IV layers and V barrel cortical neurons in rat]

Seretonergic pathway is one of the neuromodulatory mechanisms which mainly originates from dorsal raphe nucleus [DRN]. In order to explore the role of serotonin on sensory processing, we investigated the effect of DRN stimulation on response properties of the IV layer and V neurons of whisker related area of rat somatosensory cortex. In this study twenty adult male Wistar rats [250-350gr] were used. DRN was stimulated at 0, 50, 100, 200 and 400ms before principal or adjacent whiskers deflection individually or in a condition test paradigm. For assessing the effect of DRN stimulation on inhibitory receptive field of barrel neurons, adjacent whisker was also deflected 20ms before principal whisker deflection. DRN stimulation decreased the On response magnitude of layer V neurons to principal whisker deflection [p<0.05]. The On response latency of the layer IV of neurons increased when DRN was stimulated 200 or 400ms before principal whisker deflection [p<0.05 and p<0.01 respectively]. DRN stimulation had no effect on both the On response magnitude and latency of neurons to adjacent whisker deflection. We observed a decrease in inhibitory effect of adjacent whisker deflection on the magnitude of neuronal response to principal whisker deflection on the IV layer when DRN was stimulated 200ms before principal whisker deflection [p<0.05]. Our results suggest that DRN have a modulatory effect on information processing in somatosensory cortex of rats

[The effect of nitric oxide microinjection in nucleus accumbens shell on morphine withdrawal signs in male rats]

This study was performed to evaluate the effects of intra-nucleus accumbens shell microinjection of Larginine [NO precursor] and L-NAME [nitric oxide synthase [NOS] inhibitor] on morphine withdrawal signs in male rats. Rats were anaesthetized with a combination of ketamine and xylazine, and placed in stereotaxic apparatus, and a guide cannula was inserted into nucleus accumbens [Nacc] shell, [1.7 mm Anterior to bregma, 0.8 mm bilaterally to bregma and 7.1 mm depth from skull surface]. Morphine dependency was induced by subcutaneous administration of morphine [10-20 mg/kg for 5 days], and morphine withdrawal signs were precipitated by naloxone administration [4mg/kg/ip]. Rats received either single or repeated microinjections of saline, L-arginine or L-NAME into Nacc shell during the scheduled periods for 5 days. In Sham group, bilateral canulla was inserted into Nacc shell, but no drug was microinjected, and in saline group only normal saline was injected into Nacc shell in the same way as the experimental groups during the scheduled periods. Control group was intact. The results of this study showed no significant difference between control and saline treated groups in the expression of morphine withdrawal signs. Single dose microinjection of L-NAME / L-arginine, just prior to the last injection of morphine, had no effect on morphine withdrawal signs, but repeated microinjection of L-arginine / LNAME decreased jumping, rearing and weight loss [only in L-NAME group], as compared to control rats. The obtained results indicate that NO injection in Nacc shell may be involved in some of morphine withdrawal signs