Behavioural and biochemical studies of citalopram and WAY 100635 in rat chronic mild stress model.
Reversal of chronic mild stress (CMS)-induced decrease of sucrose consumption has been studied in rats after 2, 7, 14, and 35 days treatment with imipramine, citalopram (both 10 mg/kg per day, i.p.), WAY 100635 (0.2 mg/kg sc, b.i.d.), and citalopram plus WAY 100635. Bmax, Kd, and functional status [cyclic AMP (cAMP) generation] of beta1-adrenoceptors were assessed in cortical tissue at the same time points. Citalopram reversed CMS-induced reduction of sucrose intake at an earlier time point than imipramine. WAY 100635 was not effective and did not potentiate the effect of citalopram. CMS produced increase of Bmax. Imipramine decreased Bmax in controls (Days 2, 7, 14, and 35) and normalised Bmax in stressed animals (Day 35). Citalopram, WAY 100635, and the combination increased Bmax in stressed animals and controls (Days 14 and 35). Inconsistent changes of Kd values and of cAMP responses to noradrenaline (NA) stimulation were observed. Thus stress- and drug-induced effects on beta1-adrenoceptors do not appear to be a common biochemical marker of antidepressant-like activity in the CMS model.
Papp
Mariusz
M
Institute of Pharmacology, Polish Academy of Sciences, 31-343 Cracow, Poland.
Nalepa
Irena
I
Antkiewicz-Michaluk
Lucyna
L
Sánchez
Connie
C
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D002908:Chronic Disease; D015283:Citalopram / Q000378:metabolism* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D008297:Male; D010879:Piperazines / Q000378:metabolism* / Q000627:therapeutic use; D011485:Protein Binding; D011725:Pyridines / Q000378:metabolism* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013312:Stress, Physiological / Q000188:drug therapy / Q000378:metabolism*
D010879:Piperazines; D011725:Pyridines; D011943:Receptors, Adrenergic, beta; D015283:Citalopram; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide