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.
Urani
Alexandre
A
INSERM U.336, Behavioural Neuropharmacology group, Institut de Biologie, 4, bvd Henri IV, 34060 Montpellier, France.
Romieu
Pascal
P
Roman
François J
FJ
Maurice
Tangui
T
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