Biomaterial Database

Effects of short- and long-term administration of fluoxetine on the monoamine content of rat brain. 1992

S Caccia, and C Fracasso, and S Garattini, and G Guiso, and S Sarati

Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.

The effects of repeated doses of fluoxetine over time and dose-responses of the content of indoles and catecholamines and metabolism, were examined in rats in relation to the concentrations of the parent compound and its active metabolite norfluoxetine in brain. Brains were removed for assays of the regional content of monoamines and concentrations of drugs 24 hr after the last dose on days 1, 7 and 21 of a twice-daily schedule of fluoxetine (15 mg/kg, i.p.). Measurements were also taken 1 week after the last dose (7.5 and 15 mg/kg, b.i.d.) of the 21-day regimen. On day 1 fluoxetine did not change the content of serotonin (5-HT) but reduced the concentrations of 5-hydroxyindolacetic acid (5-HIAA) in the hippocampus and cortex, compatible with the action of a blocker of the uptake of 5-HT. Continued injections of fluoxetine, however, significantly reduced 5-HT in the brain of the rat, the depletion being significant on days 7 and 21 in the hippocampus and cortex, respectively. The content of indoles remained significantly decreased for at least a week after the last dose of fluoxetine in the 21-day regimen, although the concentrations of 5-HIAA (but not 5-HT) totally recovered at the smaller dose (7.5 mg/kg) in all regions of the brain (cortex, hippocampus and striatum). In spite of slight changes in the concentrations and metabolism of dopamine (DA) in the striatum, 24 hr after the last dose (15 mg/kg), treatment with drug had no significant long-term effects on the content of catecholamines in these regions of the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

UI	MeSH Term	Description	Entries
D007274	Injections, Intraperitoneal	Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall.	Intraperitoneal Injections,Injection, Intraperitoneal,Intraperitoneal Injection
D011919	Rats, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.	August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D012016	Reference Values	The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.	Normal Range,Normal Values,Reference Ranges,Normal Ranges,Normal Value,Range, Normal,Range, Reference,Ranges, Normal,Ranges, Reference,Reference Range,Reference Value,Value, Normal,Value, Reference,Values, Normal,Values, Reference
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D002540	Cerebral Cortex	The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.	Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D003342	Corpus Striatum	Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.	Lenticular Nucleus,Lentiform Nucleus,Lentiform Nuclei,Nucleus Lentiformis,Lentiformis, Nucleus,Nuclei, Lentiform,Nucleus, Lenticular,Nucleus, Lentiform,Striatum, Corpus
D004298	Dopamine	One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.	Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D004334	Drug Administration Schedule	Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.	Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D005260	Female		Females
D005473	Fluoxetine	The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants.	Fluoxetin,Fluoxetine Hydrochloride,Lilly-110140,N-Methyl-gamma-(4-(trifluoromethyl)phenoxy)benzenepropanamine,Prozac,Sarafem,Lilly 110140,Lilly110140