TY - JOUR
T1 - Chronic treatment with fluoxetine decreases cerebral metabolic responses to the 5-HT1A agonist 8-hydroxy-2(di-N-propylamino)tetralin and increases those to the 5-HT2A/2C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane and to the dopaminergic agonist apomorphine
AU - Freo, Ulderico
AU - Merico, Antonio
AU - Ermani, Mario
AU - Ori, Carlo
PY - 2010/6/4
Y1 - 2010/6/4
N2 - Fluoxetine is a selective serotonin (5-HT) reuptake inhibitor that, when given chronically, alters different neurotransmitter systems. To assess functional changes occurring in the 5-HT and dopaminergic systems, we investigated the effects of 5-HT1A agonist 8-hydroxy-2(di-N-propylamino)tetralin (8-OH-DPAT), of the 5-HT2A/2C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and of the dopamine D1/2 agonist apomorphine (APO) on behavior and on regional cerebral metabolic rates for glucose (rCMRglc) in rats pretreated for 3 weeks with saline or fluoxetine (8 mg/kg/day). Behavioral effects were assessed for 8-OH-DPAT by scoring the 5-HT syndrome, for DOI by counting head shakes and for APO with an activity monitor. rCMRglc were measured with quantitative autoradiographic [14C]2-deoxyglucose technique in 60 brain regions at 10 min after acute administration of 8-OH-DPAT 1 mg/kg, at 30 min after DOI 5 mg/kg or at 10 min after APO 1 mg/kg. Chronic fluoxetine did not alter the 5-HT syndrome by 8-OH-DPAT, decreased head shakes by DOI and enhanced hyperlocomotion by APO. 8-OH-DPAT produced rCMRglc increases in sensorimotor regions that were unaffected by fluoxetine pretreatment and diffuse metabolic decrements that were attenuated by fluoxetine in limbic and raphe areas (17% and 4% mean decreases, respectively, in saline control and fluoxetine-pretreated rats). DOI produced widespread rCMRglc declines that were intensified by fluoxetine (14% and 20% decreases, in control and fluoxetine rats). APO caused rCMRglc increases in 22 brain regions that were potentiated by fluoxetine in dopaminergic motor areas (10% and 25% increases, in control and fluoxetine rats). In conclusion, fluoxetine enhances 5-HT neurotransmission by blunting responsivity of 5-HT1A autoreceptors and increasing that of 5-HT2A/2C postsynaptic receptors and enhances dopaminergic D1/2 receptor neurotransmission.
AB - Fluoxetine is a selective serotonin (5-HT) reuptake inhibitor that, when given chronically, alters different neurotransmitter systems. To assess functional changes occurring in the 5-HT and dopaminergic systems, we investigated the effects of 5-HT1A agonist 8-hydroxy-2(di-N-propylamino)tetralin (8-OH-DPAT), of the 5-HT2A/2C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and of the dopamine D1/2 agonist apomorphine (APO) on behavior and on regional cerebral metabolic rates for glucose (rCMRglc) in rats pretreated for 3 weeks with saline or fluoxetine (8 mg/kg/day). Behavioral effects were assessed for 8-OH-DPAT by scoring the 5-HT syndrome, for DOI by counting head shakes and for APO with an activity monitor. rCMRglc were measured with quantitative autoradiographic [14C]2-deoxyglucose technique in 60 brain regions at 10 min after acute administration of 8-OH-DPAT 1 mg/kg, at 30 min after DOI 5 mg/kg or at 10 min after APO 1 mg/kg. Chronic fluoxetine did not alter the 5-HT syndrome by 8-OH-DPAT, decreased head shakes by DOI and enhanced hyperlocomotion by APO. 8-OH-DPAT produced rCMRglc increases in sensorimotor regions that were unaffected by fluoxetine pretreatment and diffuse metabolic decrements that were attenuated by fluoxetine in limbic and raphe areas (17% and 4% mean decreases, respectively, in saline control and fluoxetine-pretreated rats). DOI produced widespread rCMRglc declines that were intensified by fluoxetine (14% and 20% decreases, in control and fluoxetine rats). APO caused rCMRglc increases in 22 brain regions that were potentiated by fluoxetine in dopaminergic motor areas (10% and 25% increases, in control and fluoxetine rats). In conclusion, fluoxetine enhances 5-HT neurotransmission by blunting responsivity of 5-HT1A autoreceptors and increasing that of 5-HT2A/2C postsynaptic receptors and enhances dopaminergic D1/2 receptor neurotransmission.
KW - 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane
KW - 8-hydroxy-2(di-N-propylamino)tetralin
KW - Apomorphine
KW - Cerebral metabolism
KW - Fluoxetine
KW - Serotonin
UR - http://www.scopus.com/inward/record.url?scp=77952321608&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77952321608&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2010.03.090
DO - 10.1016/j.brainres.2010.03.090
M3 - Article
C2 - 20381465
AN - SCOPUS:77952321608
VL - 1335
SP - 24
EP - 34
JO - Brain Research
JF - Brain Research
SN - 0006-8993
ER -