title: Ketamine pre-treatment dissociates the effects of electroconvulsive stimulation on mossy fibre sprouting and cellular proliferation in the dentate gyrus.
abstract: Electroconvulsive stimulation (ECS), the experimental analogue of electroconvulsive therapy (ECT), has been shown to produce both functional and structural effects in the hippocampal formation in infrahuman species. These changes may relate to the antidepressant and cognitive effects of ECT observed in patients treated for severe depressive disorders. Recent studies have described both enhanced neurogenesis in the dentate gyrus of the hippocampus and sprouting of mossy fibre projections from granule cells. The behavioural significance of these effects remains uncertain. In this study, we examined whether ketamine, a clinically available non-competitive NMDA receptor channel blocker, could block both of these "trophic" effects. Rats were given a course of eight spaced ECS or sham treatments under either halothane or ketamine anaesthesia. The thymidine analogue bromodeoxyuridine was administered to assess the degree of hippocampal cell proliferation and mossy fibre sprouting was quantified using the Timm staining method. Pre-treatment with ketamine dissociated these effects such that mossy fibre sprouting was attenuated significantly, while cell proliferation was unaffected. This dissociation may prove useful in determining the behavioural significance of these hippocampal changes, if any, for either the antidepressant or cognitive consequences of ECT.
authors.affiliation: University of Dundee, Division of Pathology and Neuroscience, Section of Psychiatry and Behavioural Sciences, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Lamont
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: Stanwell
authors.forename: Rachel
authors.initials: R
authors.lastname: Hill
authors.forename: Ian C
authors.initials: IC
authors.lastname: Reid
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Stewart
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D004597:Electroshock / Q000379:methods*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine; D001973:Bromodeoxyuridine