The involvement of serotonergic system in the antidepressant effect of zinc in the forced swim test.
Recent preclinical data indicated the antidepressant-like activity of zinc in different tests and models of depression. The present study investigates the involvement of the serotonergic system in zinc activity in the forced swim test (FST) in mice and rats. The combined treatment of sub-effective doses of zinc (hydroaspartate, 2.5 mg Zn/kg) and citalopram (15 mg/kg), fluoxetine (5 mg/kg) but not with reboxetine (2.5 mg/kg) significantly reduces the immobility time in the FST in mice. These treatments had no influence on the spontaneous locomotor activity. Moreover, while the antidepressant-like effect of zinc (5 mg/kg) in the FST was significantly blocked by pretreatment with inhibitor of serotonin synthesis, p-chlorophenylalanine (pCPA, 3x200 mg/kg), 5HT-2(A/C) receptor antagonist, ritanserin (4 mg/kg) or 5HT-1A receptor antagonist, WAY 1006335 (0.1 mg/kg), the zinc-induced reduction in the locomotor activity was not affected by these serotonin modulator agents. These results indicate the specific involvement of the serotonergic system in antidepressant but not the motion behavior of zinc in mice. Also, an increase in the swimming but not climbing parameter of the rat FST observed following zinc administration (2.5 and 5 mg Zn/kg) indicates the serotonin pathway participation. This present data indicates that the antidepressant-like activity of zinc observed in the FST involves interaction with the serotonergic system.
Szewczyk
Bernadeta
B
Laboratory of Trace Elements Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland.
Poleszak
Ewa
E
Wlaź
Piotr
P
Wróbel
Andrzej
A
Blicharska
Eliza
E
Cichy
Agnieszka
A
Dybała
Małgorzata
M
Siwek
Agata
A
Pomierny-Chamioło
Lucyna
L
Piotrowska
Anna
A
Brański
Piotr
P
Pilc
Andrzej
A
Nowak
Gabriel
G
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D015283:Citalopram / Q000494:pharmacology; D010134:Fenclonine; D005473:Fluoxetine / Q000494:pharmacology; D008297:Male; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009942:Organometallic Compounds / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000077593:Reboxetine; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000502:physiology*; D018490:Serotonin Agents; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013550:Swimming / Q000523:psychology*; D017967:Zinc Compounds / Q000494:pharmacology*
D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D001224:Aspartic Acid; D015283:Citalopram; D010134:Fenclonine; D005473:Fluoxetine; D009025:Morpholines; D009942:Organometallic Compounds; D010879:Piperazines; D011725:Pyridines; D000077593:Reboxetine; D016713:Ritanserin; D012701:Serotonin; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; D017967:Zinc Compounds; C106152:zinc-bis(hydrogenaspartate); C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide