Cariprazine delays ouabain-evoked epileptiform spikes and loss of activity in rat hippocampal slices

• Published in: Psychiatry research Vol. 229; no. 1; pp. 370 - 373
• Main Authors: El-Mallakh, Rif S, Payne, Ralphiel S, Schurr, Avital, Gao, Yonglin, Lei, Zhemin, Kiss, Béla, Gyertyán, István, Adham, Nika
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 30.09.2015
• Subjects: Animals; Antipsychotic; Antipsychotic Agents - pharmacology; Bipolar disorder; Bipolar Disorder - drug therapy; Dopamine antagonists; Dopamine D3; Evoked Potentials - drug effects; Hippocampus - drug effects; Hippocampus - physiopathology; Male; Mania; Ouabain - adverse effects; Piperazines - pharmacology; Psychiatry; Rapid cycling; Rats; Rats, Sprague-Dawley; Receptors; Rapid cycling; Receptors; Dopamine antagonists; Mania; Bipolar disorder; Antipsychotic; Dopamine D 3; Dopamine D3; Dopamine D
• ISSN: 0165-1781; 1872-7123
• DOI: 10.1016/j.psychres.2015.05.114

Abstract In the only bipolar cycling in vitro model, rat hippocampal slices are treated with the sodium pump inhibitor ouabain, which induces epileptiform activity, followed by refractory activity loss that recovers and cycles back to epileptiform activity. Thus, clinical cycling seen in patients with bipolar disorder is modeled on a cellular level as alternating hyperactivity and hypoactivity interspersed with normal activity. In this study, we tested the ability of cariprazine a new antipsychotic candidate to block ouabain-induced changes in rat hippocampal slices. Cycling of population spikes and epileptiform bursts was evoked using an extracellular stimulation electrode located in the Schaeffer collaterals of 400-µm-thick rat hippocampal slices treated with ouabain (3.3 μM) alone or in combination with cariprazine (1, 5, 25, and 50 µM). Responses were recorded using an extracellular electrode placed in the cell body layer of the CA1 region. Cariprazine 25 and 50 µM delayed ouabain-induced epileptiform burst onset and subsequent activity loss. Lower cariprazine concentrations were ineffective. Cariprazine delays the onset of ouabain-induced epileptiform bursts and the loss of spiking activity similarly to that previously demonstrated with the mood stabilizer lithium. These results suggest that cariprazine may have therapeutic potential for treatment of bipolar disorder.