Behavioral effects of 8-OH-DPAT: studies using the Microtaxic ventricular injector.
This study introduces the Microtaxic Ventricular Injector, a plastic mold that allows for the rapid administration of drugs into the ventricular system of adult rats. The Microtaxic Ventricular Injector was used to destroy serotonin (5-HT) neurons by administering the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT; 100 micrograms/10 microliters) into the lateral cerebroventricles. Injection of the 5-HT neurotoxin produced a 79% depletion of 5-HT in the cortex and an 86% depletion of 5-HT in the hippocampus. In addition, 5,7-DHT treatment produced a two-fold shift to the left of the dose-response curve of the 5-HT1A agonists 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) or 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) in producing the 5-HT syndrome indicating the development of denervation supersensitivity following the destruction of 5-HT neurons. In addition, the behavioral effects of 8-OH-DPAT were studied when administered to different CNS sites using the Microtaxic Ventricular Injector. 8-OH-DPAT (10 micrograms) injected into the fourth ventricle produced the 5-HT syndrome in 100% of the rats tested within a 3 min time period. In contrast, 8-OH-DPAT injected into the lateral ventricle produced the syndrome in only 33% of the rats tested and with a 6-9 min delay until this effect occurred. These results indicate the greater potency of 8-OH-DPAT at producing the 5-HT syndrome when administered in ventricular sites that are close to its locus of action in the brainstem/spinal cord region. These experiments demonstrate the usefulness and reliability of the Microtaxic Ventricular Injector as an instrument for rapidly injecting drugs directly into different cerebroventricular sites.
Wieland
S
S
Department of Psychiatry, University of Pennsylvania, Philadelphia 19104-4283.
Goodale
D
D
Lucki
I
I
D015116:5,7-Dihydroxytryptamine / Q000008:administration & dosage; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007276:Injections, Intraventricular / Q000295:instrumentation* / Q000379:methods; D008297:Male; D009281:Naphthalenes / Q000008:administration & dosage*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D013238:Stereotaxic Techniques; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage*
D009281:Naphthalenes; D013764:Tetrahydronaphthalenes; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin