Antidepressant effect of pramipexole in mice forced swimming test: A cross talk between dopamine receptor and NMDA/nitric oxide/cGMP pathway.
Pramipexole is a dopamine D2 receptor agonist indicated for treating Parkinson disorder. This study was aimed to investigate the effect of pramipexole in forced swimming test (FST) in mice and the possible involvement of activation of D2 receptors and inhibition of N-methyl-d-aspartate (NMDA) receptors and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) on this effect. Intraperitoneal administration of pramipexole (1-3mg/kg) reduced the immobility time in the FST similar to fluoxetine (20mg/kg, i.p.). This effect of pramipexole (1mg/kg, i.p.) was ceased when mice were pretreated with haloperidol (0.15mg/kg, i.p,) and sulpiride (5mg/kg, i.p) as D2 receptor antagonists, NMDA (75mg/kg,i.p.), l-arginine (750mg/kg, i.p., a substrate for nitric oxide synthase) or sildenafil (5mg/kg, i.p., a phosphodiesterase 5 inhibitor). The administration of MK-801 (0.05mg/kg, i.p., a NMDA receptor antagonist) l-NG-Nitro arginine methyl ester (l-NAME, 10mg/kg, i.p., a non-specific nitric oxide synthase (NOS) inhibitor), 7-nitroindazole (30mg/kg, i.p., a neuronal NOS inhibitor) and methylene blue (10mg/kg, i.p.), an inhibitor of both NOS and soluble guanylyl cyclase (sGC) in combination with the sub-effective dose of pramipexole (0.3mg/kg, i.p.) reduced the immobility. Altogether, our data suggest that the antidepressant-like effect of pramipexole is dependent on the activation of D2 receptor and inhibition of either NMDA receptors and/or NO-cGMP synthesis. These results contribute to the understanding of the mechanisms underlying the antidepressant-like effect of pramipexole and reinforce the role of D2 receptors, NMDA receptors and l-arginine-NO-GMP pathway in the antidepressant mechanism of this agent.
Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Sattar
S
Ostadhadi
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, International Campus, Tehran University of Medical Sciences, Tehran, Iran.
Muhammad
M
Imran Khan
Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
Abbas
A
Norouzi-Javidan
Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: Dehpour@sina.tums.ac.ir.
Ahmad-Reza
AR
Dehpour
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001120:Arginine / Q000494:pharmacology; D052160:Benzothiazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006152:Cyclic GMP / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D007103:Immobilization; D007274:Injections, Intraperitoneal; D008297:Male; D008751:Methylene Blue / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D016202:N-Methylaspartate / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D000077487:Pramipexole; D011954:Receptors, Dopamine / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000068677:Sildenafil Citrate / Q000494:pharmacology; D013550:Swimming / Q000502:physiology*
D000928:Antidepressive Agents; D052160:Benzothiazoles; D011954:Receptors, Dopamine; D009569:Nitric Oxide; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D000077487:Pramipexole; D001120:Arginine; D000068677:Sildenafil Citrate; D006152:Cyclic GMP; D006220:Haloperidol; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester
Depression; Dopamine D2 receptor; Forced swimming test; Mice; NMDA; Nitric oxide; Pramipexole