Enhanced antidepressant effect of sigma(1) (sigma(1)) receptor agonists in beta(25-35)-amyloid peptide-treated mice.
This study examined the antidepressant efficacy of the selective sigma(1) receptor agonists igmesine or PRE-084 in mice injected intracerebroventricularly (i.c.v.) with beta(25-35)-amyloid peptide and submitted to the forced swim test. Beta(25-35) peptide-injected animals developed memory deficits after 8 days contrarily to controls injected with scrambled beta(25-35) peptide or vehicle solution. In the forced swim test, the i.c.v. treatment failed to affect the immobility duration, but the antidepressant effect of the sigma(1) agonists was facilitated in beta(25-35) animals. Igmesine reduced immobility duration at 30 versus 60 mg/kg in control groups. PRE-084 decreased immobility duration at 30 and 60 mg/kg only in beta(25-35) animals. Desipramine reduced the immobility duration similarly among groups and fluoxetine appeared less potent in beta(25-35) animals. The beta(25-35) animals exhibited decreased progesterone levels in the hippocampus (-47%). The behavioural efficacy of sigma(1) agonists is known to depend on neuro(active)steroids levels synthesised by glial cells and neurones, which are affected by the beta-amyloid toxicity. This behavioural study suggests that sigma(1) agonists, due to their enhanced efficacy, may allow to alleviate the depressive symptoms associated with Alzheimer's disease.
INSERM U.336, Behavioural Neuropharmacology group, Institut de Biologie, 4, bvd Henri IV, 34060 Montpellier, France.
Alexandre
A
Urani
Pascal
P
Romieu
François J
FJ
Roman
Tangui
T
Maurice
D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D002934:Cinnamates / Q000494:pharmacology; D003521:Cyclopropanes / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011374:Progesterone / Q000378:metabolism; D017480:Receptors, sigma / Q000819:agonists*; D013315:Stress, Psychological / Q000523:psychology; D013550:Swimming / Q000523:psychology; D000097605:Sigma-1 Receptor
D016229:Amyloid beta-Peptides; D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D002934:Cinnamates; D003521:Cyclopropanes; D003891:Desipramine; D005473:Fluoxetine; D009025:Morpholines; D010446:Peptide Fragments; D011374:Progesterone; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C113041:amyloid beta-protein (35-25); C071738:2-(4-morpholino)ethyl-1-phenylcyclohexane-1-carboxylate; C065310:igmesine