ABSTRACT
CONTEXT: Neuropsychiatric disorders, like anxiety and depression, are global problems for clinical researchers in neurology. Recently, some authors have shown neuroprotective and anti-inflammatory effects of Scrophularia striata Boiss (Scrophulariaceae) extract in rodents. OBJECTIVE: The purpose of the current study was to investigate the effects of S. striata extract on anxiety and depressant-like behaviors and find a possible mechanism for these impacts. MATERIALS AND METHODS: In this study, the elevated plus-maze (EPM) and forced swimming test (FST), which are useful models for selective identification of anxiolytic and antidepressant drug effects in rodents, were used. We investigated the effects of S. striata ethanol extract at different doses (20, 50, 100, 160 and 220 mg/kg) on anxiety and depression behaviors in the EPM and FST, and then we assessed the role of γ-aminobutyric acid (GABA)A receptor in modulation of the effects of S. striata extract in the brain. RESULTS: Our results showed that effective doses of S. striata (100 and 160 mg/kg) increased the percentages of open arm time and entries in the EPM and decreased immobility time in the FST in comparison with control group, indicating anxiolytic and antidepressant effects, respectively. Moreover, intracerebroventricular administration of GABAA receptor agonist (muscimol; 1 µg/rat) enhanced the impact of S. striata, and GABAA receptor antagonist (bicuculline; 1 µg/rat) blocked these effects in rats, indicating that significant interactions existed between S. striata and the GABAergic system in the brain. DISCUSSION AND CONCLUSION: Findings of this study suggest that anxiolytic and antidepressant effects of S. striata may be modulated via the GABAergic system.
Subject(s)
Anti-Anxiety Agents/pharmacology , Antidepressive Agents/pharmacology , Plant Extracts/pharmacology , Scrophularia/chemistry , Animals , Anti-Anxiety Agents/administration & dosage , Anti-Anxiety Agents/isolation & purification , Antidepressive Agents/administration & dosage , Antidepressive Agents/isolation & purification , Anxiety/drug therapy , Anxiety/physiopathology , Bicuculline/pharmacology , Brain/drug effects , Brain/metabolism , Depression/drug therapy , Depression/physiopathology , Disease Models, Animal , Dose-Response Relationship, Drug , Injections, Intraventricular , Male , Maze Learning/drug effects , Muscimol/pharmacology , Plant Extracts/administration & dosage , Rats , Rats, Wistar , Receptors, GABA-A/drug effects , Receptors, GABA-A/metabolism , Swimming/psychologyABSTRACT
Phencyclidine (1-(1-phenylcyclohexyl)piperidine, CAS 956-90-1, PCP, I) and many of its analogues have shown some pharmacological effects. In this study, new pyrrole derivatives of I (1-(1-phenylcyclohexyl)pyrrole, II and 1-[1-(4-methylphenyl)(cyclohexyl)]pyrrole, III) and their intermediates were synthesized and the acute and chronic pains were examined on mice using tail immersion (as a model of acute thermal pain) and formalin (as a model of acute and chronic chemical pain) tests and the results were compared with the PCP and control groups. The results indicated that III generated higher analgesic effects in the tail immersion test compared to the PCP and control (dimethyl sulfoxide, DMSO) groups, demonstrating a marked and significant increase in tail immersion latency, but this effect was not observed for II in the dose of 1 mg/kg. The formalin test showed that III was effective in acute chemical pain (phase I, 0-5 min after injection), but was not effective for II at the same dosage compared to the PCP and control groups. Also chronic pain will be significantly attenuated by III but II was not effective as compared to the other groups. It is concluded that substitution of the aromatic pyrrole ring instead of piperidine in the PCP molecule will not be effective alone in tail immersion and formalin tests but the addition of a methyl group (with high electron donating and dipole moments) on the phenyl group plus substitution of the aromatic pyrrole ring can be effective in acute and chronic pain compared to the PCP and control groups.
