Neurochemical changes in pigeon cerebrospinal fluid during chronic administration of buspirone or 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT).
Cerebrospinal fluid (CSF), collected repeatedly from White Carneau pigeons chronically implanted with guide cannulae located in the lateral ventricles, was analyzed for metabolites of serotonin, dopamine and norepinephrine after acute and chronic administration of buspirone or 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Following the acute administration of 3.0 mg/kg buspirone, levels of 5-hydroxyindoleacetic acid (5-HIAA) decreased, while increases occurred in the dopamine metabolites homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC). Decreases in 5-HIAA persisted throughout the chronic dosing regimen (36 days), while dopamine metabolites returned to control levels within 8 days. When chronic buspirone was discontinued, levels of 5-HIAA were restored to predrug control levels, while levels of HVA, DOPAC and 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) decreased. All metabolites returned to predrug control levels within one week following buspirone discontinuation except for MHPG, which remained depressed. When the acute effects of buspirone were reexamined, levels of 5-HIAA were again significantly decreased, while HVA and DOPAC levels, as well as those of MHPG, increased significantly. Acute administration of the 5-HT1A receptor ligand 8-OH-DPAT (3.0 mg/kg) resulted in large decreases in 5-HIAA levels that persisted throughout the period of chronic administration. Neither acute nor daily administration of 8-OH-DPAT changed levels of HVA, DOPAC or MHPG. Large increases in 5-HIAA occurred when chronic 8-OH-DPAT was discontinued but declined within one week to control levels. Following a two-week drug-free period, 8-OH-DPAT again caused a significant reduction in 5-HIAA levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Nader
M A
MA
Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
Barrett
J E
JE
D015102:3,4-Dihydroxyphenylacetic Acid / Q000134:cerebrospinal fluid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D002065:Buspirone / Q000008:administration & dosage / Q000494:pharmacology*; D010856:Columbidae; D004298:Dopamine / Q000134:cerebrospinal fluid*; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D009638:Norepinephrine / Q000134:cerebrospinal fluid*; D012701:Serotonin / Q000134:cerebrospinal fluid*; D013238:Stereotaxic Techniques; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000494:pharmacology*
D009281:Naphthalenes; D013764:Tetrahydronaphthalenes; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002065:Buspirone; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid