THE EFFECTS OF CHRONIC IMIPRAMINE ADMINISTRATION ON RAT BRAIN LEVELS OF SEROTONIN, 5-HYDROXYINDOLEACETIC ACID, NOREPINEPHRINE AND DOPAMINE

¹ Thudichum Psychiatric Research Laboratory, Galesburg State Research Hospital, Galesbury, Illinois

The effects of chronic imipramine admimlistration on levels of serotonin, 5-hydroxyin doleacetic acid (5-HIAA), norepinephrine and dopamine in six areas of the brain were studied in four groups of female rats; 1) a noninjected. nonhandled group; 2) animals injected i.p. with 0.9% saline for 10 days; 3) animals injected with imipramine HCI for 10 clays (20 mg/kg i.p. daily); and 4) animals receiving imipramine HCI with food (approximately 20 mg/kg daily) for 19 days. Levels of the monoamines and 5-HIAA were determined by fluorometric analyses subsequent to the solvent extraction of these compounds from brain tissues. Compared to the nontreated group, animals given imipramine HCI either by injection or in food had significantly reduced levels of 5-HIAA in most brain areas. 5-HIAA levels were unchanged in the saline-treated group except for the reduced amounts found in the pons-medulla oblongata. Tile amimals fed imipramine had significantly reduced concemltrations of serotonin in the hippocampus, mesodien cephalon and pomis-medulla. Similar decreases, probably drug related, were also found in the imipramine-injected group. However, the extent of the drug-induced changes in the latter group was somewhat obscured by the diminution of serotonin in the cortex and medulla by saline injections only. Norepinephrine levels in the three groups of treated animals did not differ significantly from those of the nontreated group. All three schedules of treatment diminished levels of striatal dopamine. In contrast, imipramine-treated animals had significantly increased levels of dopamine in the cerebellum and the ponsmedulla oblongata.

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