Influence of serotonin 5-HT(7) receptor blockade on the behavioral and neurochemical effects of imipramine in rats.
Journal Title: Pharmacological Reports - Year 2008, Vol 60, Issue 4
Abstract
The aim of the present study was to examine the effect of the selective 5-HT(7) receptor antagonist (2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine (SB-269970), administered alone or in combination with imipramine, on the immobility time of rats in the forced swim test as well as on the extracellular levels of dopamine (DA), noradrenaline (NA), serotonin (5-HT) and their metabolites in the prefrontal cortex of freely moving rats. Both compounds were administered intraperitoneally (ip). Like imipramine (30 mg/kg, but not 20 mg/kg), SB-269970 (1.25 and 2.5 mg/kg, but not 0.625 mg/kg) significantly shortened the immobility time of rats without affecting their exploratory locomotor activity measured in the open field test. SB-269970 (0.625 and 1.25 mg/kg) raised the extracellular levels of DA, NA, 5-HT and their metabolites in rat prefrontal cortex. In that structure, imipramine (20 mg/kg) produced an increase in all the neurotransmitters measured, but failed to affect the levels of their metabolites. A combination of the inactive doses of SB-269970 (0.625 mg/kg) and imipramine (20 mg/kg) found in the forced swim test produced antidepressant-like effect, which did not stem from the increased exploratory locomotor activity. At the same time, that combination voked a vast increase in the output of NA - but not DA and 5-HT - compared to the effects of both those drugs given alone. These results open up a possibility that the stimulating effect of SB-269970 on DA, NA and 5-HT transmission in the prefrontal cortex plays some role in the antidepressant-like activity of this compound. Moreover, these findings suggest that the increase in cortical NA level seems to account for the anti-immobility action observed after joint administration of the selective 5-HT(7) receptor antagonist and imipramine in rats.
Authors and Affiliations
Anna Wesołowska, Magdalena Kowalska
Keywords
Related Articles
- EP ID EP113019
- DOI -
- Views 90
- Downloads 0
COX-2 as a target for cancer chemotherapy.
Cyclooxygenase-1 and -2 (COX-1/2) catalyze the initial step in the formation of prostaglandins. Very recently their role in carcinogenesis has become more evident. They influence apoptosis, angiogenesis, and invasion, an...
Effects of three calcium channel antagonists (amlodipine, diltiazem and verapamil) on the protective action of lamotrigine in the mouse maximal electroshock-induced seizure model.
The aim of this study was to assess the effect of three calcium channel antagonists (amlodipine, diltiazem and verapamil) on the anticonvulsant action of lamotrigine (a second generation antiepileptic drug) against maxim...
Antinociceptive synergy between diclofenac and morphine after local injection into the inflamed site.
Background: Combinations of non-steroidal anti-inflammatory drugs with opioids are frequently used to reduce opioid doses required in the clinical management of acute pain. The present study was designed to evaluate the...
Effect of thymoquinone on the lung pathology and cytokine levels of ovalbumin-sensitized guinea pigs.
Different pharmacological effects from Nigella sativa have been demonstrated in guinea pig tracheal chains in previous studies. In the present study, the prophylactic effects of thymoquinone on lung pathology as well as...
Neonatal co-lesion by DSP-4 and 5,7-DHT produces adulthood behavioral sensitization to dopamine D(2) receptor agonists.
To assess the possible modulatory effects of noradrenergic and serotoninergic neurons on dopaminergic neuronal activity, the noradrenergic and serotoninergic neurotoxins DSP-4 N-(2-chlorethyl)-N-ethyl-2-bromobenzylamine...