ABSTRACT
The influence of GABA agonists and antagonists on analgesic activity of imipramine (IMA, 20 mg/kg, ip) was studied using the hotplate method. Administration of GABAA receptor agonist muscimol (1 mg/kg, ip), GABAB receptor agonist baclofen (3 mg/kg, ip) or GABA-T inhibitor aminooxyacetic acid (25 mg/kg, ip) increased the analgesic effect of IMA. On the other hand pretreatment of GABAA receptor antagonist bicucukline (2 mg/kg ip), GABAB receptor antagonist delta-amino-n-valeric acid (50 mg/kg, ip) or GABA synthesis inhibitor thiosemicarbazide (50 mg/kg, ip) attenuated the IMA analgesia. These results suggest that the analgesic action of IMA may be mediated by functional alteration of a central GABAergic mechanism and/or subsequent stimulation of GABA receptors.
Subject(s)
4-Aminobutyrate Transaminase/antagonists & inhibitors , Analgesics, Non-Narcotic/pharmacology , Animals , Antidepressive Agents, Tricyclic/pharmacology , Enzyme Inhibitors/pharmacology , Female , GABA Agents/pharmacology , GABA Agonists/pharmacology , GABA Antagonists/pharmacology , Imipramine/pharmacology , Injections, Intraperitoneal , Male , Mice , Receptors, GABA-A/antagonists & inhibitors , Receptors, GABA-B/antagonists & inhibitorsABSTRACT
In the forced swimming induced immobility test, neuropeptide FMRFamide (5-20 micrograms) administered via the intracerebroventricular (icv) route, prolonged immobilization period in rats. On the other hand, immunoneutralization of endogenous FMRFamide by its antiserum (1 microliter, icv) significantly reduced the duration of immobility. Intraperitoneal administration of amitriptyline (3 mg/kg), imipramine (5 mg/kg), fluoxetine (5 mg/kg) or amphetamine (0.5 mg/kg) attenuated FMRFamide-induced prolongation of immobility. Biochemical studies indicated that FMRFamide treatment had significant effects on rat brain monoamines. FMRFamide significantly lowered the brain levels of 5-hydroxytryptamine and norepinephrine in the doses that prolonged the immobility. These results that FMRFamide prolongs the duration of immobility, perhaps by modulating the release of neurotransmitters like 5-hydroxytryptamine and/or norepinephrine.
Subject(s)
Amino Acid Sequence , Animals , Antidepressive Agents/pharmacology , Brain/drug effects , FMRFamide , Immobilization , Injections, Intraventricular , Male , Molecular Sequence Data , Neuropeptides/administration & dosage , Norepinephrine/metabolism , Rats , Serotonin/metabolismABSTRACT
The possible role of centrally administered tetrapeptide FMRFamide (Phe-Met-Arg-Phe-NH2) on gastric acid secretion in pylorus ligated rats was investigated. Intracerebroventricularly administered FMRFamide stimulated the gastric acid secretion in a dose-dependent manner. This stimulatory effect was abolished by vagotomy and atropine pretreatment. The presence of FMRFamide in rat brain and the ability of FMRFamide to stimulate gastric acid secretion suggest that FMRFamide plays a physiological role in brain modulation of gastric acid secretion.
Subject(s)
Amino Acid Sequence , Animals , FMRFamide , Gastric Acid/metabolism , Injections, Intraventricular , Male , Molecular Sequence Data , Neuropeptides/administration & dosage , Neurotransmitter Agents/administration & dosage , RatsABSTRACT
The influence of calcium channel blockers (CCB) on the analgesic activity of tricyclic antidepressants (TCA) was examined using hot plate (thermal) and writhing (chemical) method. Intraperitoneal injections of TCA, imipramine and amitriptyline or CCB viz: verapamil, nifedipine, nicardipine and cinnarizine per se produced analgesia. The Analgesic effect of TCA was further enhanced by prior treatment with CCB. The increase in TCA analgesia could not be ascribed to unitary mechanism but could possibly be mediated by opioid and/or nonopioid systems. These results clearly provide an evidence that a combination treatment of CCB and TCA may permit reduction of the TCA doses while treating chronic pain of organic origin.