title: The selective sigma2 ligand Lu 28-179 has an antidepressant-like profile in the rat chronic mild stress model of depression.
abstract: The selective sigma2 (sigma2) ligand Lu 28-179, or 1'-[4[1-(4-fluorophenyl)-1H-indol-3-yl]-l-butyl]spiro[isobenzofuran++ +-1(3H),4'-piperidine], was studied in the chronic mild stress (CMS) model of depression. The CMS test procedure consists of sequential exposures to a variety of mild stressors for a prolonged period of time and results in behavioural hedonic deficits, which can be measured as decreased consumption of a palatable sucrose solution. In rats, exposure to CMS treatment with citalopram or imipramine for 2 or 4 weeks, respectively, normalized the sucrose intake. Similarly, Lu 28-179 (1.0 mg/kg subcutaneously per day) normalized sucrose intake in rats exposed to CMS. This effect was found in two separate experiments and was achieved after 3 and 4 weeks of treatment, respectively. This suggests an antidepressant potential for Lu 28-179. Doses of 0.01 and 0.1 mg/kg were inactive. Groups exposed to CMS and treated with 0.5, 2.0 or 3.0 mg/kg showed a significantly increased sucrose intake compared with vehicle-treated stressed animals at week 5. However, this effect was confounded by decreased intake in the vehicle controls. Lu 28-179 did not affect sucrose intake in non-stressed rats at any of the doses tested.
authors.affiliation: Pharmacological Research, Copenhagen, Denmark. cs@lundbeck.com
authors.forename: C
authors.initials: C
authors.lastname: Sánchez
authors.forename: M
authors.initials: M
authors.lastname: Papp
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002908:Chronic Disease; D015283:Citalopram / Q000494:pharmacology; D003863:Depression / Q000209:etiology / Q000523:psychology*; D004435:Eating / Q000187:drug effects; D007099:Imipramine / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000187:drug effects*; D013141:Spiro Compounds / Q000494:pharmacology*; D013315:Stress, Psychological / Q000150:complications / Q000523:psychology*; D013395:Sucrose
chemical_list: D014151:Anti-Anxiety Agents; D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D007211:Indoles; D008024:Ligands; C109644:Lu 28-179; D017480:Receptors, sigma; D013141:Spiro Compounds; C106107:sigma-2 receptor; D015283:Citalopram; D013395:Sucrose; D007099:Imipramine