Tehran University Medical Journal

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Background: Calcium channel blockers have an important role in treatment of various cardiovascular diseases including hypertension, angina pectoris and cardiac arrhythmias, so study of cardiovascular effects of derivatives of these drugs are useful. Nifedipine is one of these drugs that used widely to treat hypertension and other cardiovascular diseases. The aim of the present study was to evaluate the central effects of synthesized dihydropyridine derivatives on systolic blood pressure and heart rate of rats and comparison to nifedipine. Methods: Sixty four male rats, after induction of anesthesia and intracerebral ventricu-lar cannulation using stereotaxis method, were divided into eight equal groups. One week after the stereotaxis surgery, the systolic blood pressure and heart rate were eval-uated in times 15 to 60 minutes after intracerebral ventricular injection of DMSO (di-methylsulfoxide) and nifedipine in doses of 80 to 320 microgram/rat and also three synthesized dihydropyridine derivatives (A, B and C) in dose of 240 microgram/rat. Effects of these drugs on systolic blood pressure and heart rate were analyzed using two way repeated measure ANOVA statistical test, followed by Bonferroni posthoc test. All data were considered significant at P<0.05. Results: The inhibitory effects of derivative B on systolic blood pressure and heart rate in dose of 240 microgram/rat in times of 15 and 30 minutes after injection were more potent than nifedipine (P<0.001), while A and C derivatives showed weaker inhibitory properties, compared with nifedipine. Also the inhibitory effects of derivative B on heart rate in dose of 240 microgram/rat were stronger than nifedipine in times of 15 to 60 minutes after injection (P<0.05). Conclusion: Novel dihydropyridine derivatives can possess more potent and stable in-hibitory effects on systolic blood pressure and heart rate, and some part of these properties at least, can be attributed to their direct inhibitory effects on brain neurons.

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Background: As a psychoactive plant, Cannabis sativa (Marijuana) is widely used throughout the world. Several investigations have indicated that administration of Marijuana affects various cognitive and non-cognitive behaviors. These include anxiety-like behaviors and learning and memory deficit. It has been shown that three main cannabinoid receptors [i.e. CB1, CB2 and CB3 are involved in cannabinoids’ functions. CB1 receptors are abundantly expressed in the central nervous system regions such as hippocampus, amygdala, cerebellum and the cortex. Therefore, the neuropsychological functions of endocannabinoids are thought to be more linked to CB1 receptors. Among other brain regions, CB1 is highly expressed in the amygdala which is an integral component of the limbic circuitry. The amygdala plays a major role in the control of emotional behavior, including conditioned fear and anxiety. In present study we examined the possible roles of basolateral amygdala (BLA) GABA_B receptors in arachydonilcyclopropylamide (ACPA)-induced anxiolytic-like effect and aversive memory deficit in adult male mice.

Methods: This experimental study was conducted from September 2013 to December 2014 in Institute for Studies in Theoretical Physics and Mathematics, School of Cognitive Sciences, Tehran and Male albino NMRI mice (Pasture Institute, Iran), weighting 27-30 g, were used. Bilateral guide-cannulae were implanted to allow intra BLA microinjection of the drugs. We used Elevated Plus Maze (EPM) to examine memory and anxiety behavior (test-retest protocol). ACPA administrate intra-peritoneal and GABAB agonist and antagonist administrated intra-amygdala.

Results: Data showed that pre-test treatment with ACPA induced anxiolytic-like and aversive memory deficit The results revealed that pre-test intra-BLA infusion of baclofen (GABA_B receptor agonist) impaired the aversive memory while phaclofen (GABA_B receptor antagonist) improved it. Interestingly, pretreatment with a sub-threshold dose of baclofen reversed and potentiated anxiolytic-like effect and aversive memory deficit induced by ACPA, respectively. Conversely, similar effect with sub-threshold dose of phaclofen showed that this drug only restored aversive memory deficit but did not alter anxiolytic-like effect induced by ACPA.

Conclusion: Data indicated that BLA GABA_B receptors have critical and different roles in anxiolytic-like effect and aversive memory deficit induced by ACPA.