Cholinergic mechanisms in depression

Evidence supporting a cholinergic hypothesis of depression is presented. First, cholinergic overdrive produces behavioral, neuroendocrine, and polysomnographic features of melancholia, and melancholics exhibit state-independent supersensitivity to cholinergic overdrive. Drugs inducing up-regulation and supersensitivity of cholinergic systems produce behavioral, polysomnographic, and neuroendocrine effects of melancholia when withdrawn. These observations also implicate cholinergic system supersensitivity as a factor in the pathophysiology of certain affective disorders. Cholinergic and monoaminergic mechanisms reciprocally regulate drive-reduction, and substances of abuse either activate monoaminergic networks or antagonize cholinergic systems. These points are consistent with the hypothesis that dynamic interaction between cholinergic and monoaminergic systems is involved in the regulation of mood and affect. Finally, antimuscarinic agents have antidepressant effects. Thus, the hypothesis that supersensitivity of cholinergic systems is involved in the pathophysiology of affective disorders is supported by several lines of evidence. This evidence is reviewed; directions for future research and promising methods of investigation are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26059/1/0000133.pd

Diets rich in eicosapentaenoic acid and γ-linolenic acid affect phospholipid fatty acid composition and production of prostaglandins E1, E2 and E3 in turbot (Scophthalmus maximus), a species deficient in Δ5 fatty acid desaturase

Duplicate groups of juvenile turbot, (Scophthalmus maximus), were fed diets containing either Marinol K (MO), a marine fish oil rich in eicosapentaenoic acid (EPA; 20:5, n-3) or borage oil (BO), rich in γ-linolenic acid (GLA; 18:3, n-6), for a period of 12 weeks. Individual phospholipid fatty acid compositions from hearts of fish fed BO had significantly more 18:2, n-6, GLA, 20:2, n-6, dihomo-γ-linolenic acid (DHGLA; 20:3, n-6) and total n-6 polyunsaturated fatty acids (PUFA), but significantly less arachidonic acid (AA; 20:4, n-6), compared to fish fed MO. In both phosphatidylcholine (PC) and phosphatidylethanolamine (PE) from heart, the DHGLA was increased by over 50-fold in fish fed BO while AA was reduced by over two-thirds, compared to fish fed MO. In brain, EPA was the major C20 PUFA, i.e. potential eicosanoid precursor in all phospholipids from fish fed MO, with the EPA level being twice that of AA in brain phosphatidylinositol (PI). DHGLA was the major C20 PUFA in all phospholipid classes from fish fed BO. In kidney and gill, EPA was the predominant C20 PUFA in all phospholipid classes, except PI, in fish fed MO. In kidney of fish fed BO, DHGLA was the major C20 PUFA in all phospholipid classes, except PE. In gill of fish fed BO, DHGLA was the major C20 PUFA in all phospholipid classes, including PI, where DHGLA was over 2.5-fold greater than AA. In homogenates of heart, kidney and gill from BO-fed fish the prostaglandin E1 (PGE1) concentration was significantly increased compared to MO-fed fish. In heart and kidney homogenates from fish fed MO the PGE3 concentration was significantly increased compared to fish fed BO. The ratio of PGE2/PGE1 was significantly reduced in brain, heart, kidney and gill homogenates from fish fed BO compared to those fed MO