Amphetamine and mCPP effects on dopamine and serotonin striatal in vivo microdialysates in an animal model of hyperactivity.
In the neonatally 6-hydroxydopamine (6-OHDA)-lesioned rat hyperlocomotor activity, first described in the 1970s, was subsequently found to be increased by an additional lesion with 5,7-dihydroxytryptamine (5,7-DHT) (i.c.v.) in adulthood. The latter animal model (i.e., 134 microg 6-OHDA at 3 d postbirth plus 71 microg 5,7-DHT at 10 weeks; desipramine pretreatments) was used in this study, in an attempt to attribute hyperlocomotor attenuation by D,L-amphetamine sulfate (AMPH) and m-chlorophenylpiperazine di HCl (mCPP), to specific changes in extraneuronal (i.e., in vivo microdialysate) levels of dopamine (DA) and/or serotonin (5-HT). Despite the 98-99% reduction in striatal tissue content of DA, the baseline striatal microdialysate level of DA was reduced by 50% or less at 14 weeks, versus the intact control group. When challenged with AMPH (0.5 mg/kg), the microdialysate level of DA went either unchanged or was slightly reduced over the next 180 min (i.e., 20 min sampling), while in the vehicle group and 5,7-DHT (alone) lesioned group, the microdialysate level was maximally elevated by approximately 225% and approximately 450%, respectively--and over a span of nearly 2 h. Acute challenge with mCPP (1 mg/kg salt form) had little effect on microdialysate levels of DA, DOPAC and 5-HT. Moreover, there was no consistent change in the microdialysate levels of DA, DOPAC, and 5-HT between intact, 5-HT-lesioned rats, and DA-lesioned rats which might reasonably account for an attenuation of hyperlocomotor activity. These findings indicate that there are other important neurochemical changes produced by AMPH- and mCPP-attenuated hyperlocomotor activity, or perhaps a different brain region or multiple brain regional effects are involved in AMPH and mCPP behavioral actions.
Nowak
Przemyslaw
P
Department of Pharmacology, Medical University of Silesia, H. Jordana 38, 41-808 Zabrze, Poland.
Bortel
Aleksandra
A
Dabrowska
Joanna
J
Oswiecimska
Joanna
J
Drosik
Marzena
M
Kwiecinski
Adam
A
Opara
Józef
J
Kostrzewa
Richard M
RM
Brus
Ryszard
R
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D015115:5,6-Dihydroxytryptamine / Q000633:toxicity; D000367:Age Factors; D000661:Amphetamine / Q000633:toxicity*; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000139:chemically induced* / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D016627:Oxidopamine / Q000633:toxicity; D010879:Piperazines / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000633:toxicity*; D013565:Sympatholytics / Q000633:toxicity
D000697:Central Nervous System Stimulants; D010879:Piperazines; D017366:Serotonin Receptor Agonists; D013565:Sympatholytics; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D016627:Oxidopamine; D000661:Amphetamine; C015068:1-(3-chlorophenyl)piperazine; D004298:Dopamine; D015115:5,6-Dihydroxytryptamine