title: Neonatal co-lesion by DSP-4 and 5,7-DHT produces adulthood behavioral sensitization to dopamine D(2) receptor agonists.
abstract: To assess the possible modulatory effects of noradrenergic and serotoninergic neurons on dopaminergic neuronal activity, the noradrenergic and serotoninergic neurotoxins DSP-4 N-(2-chlorethyl)-N-ethyl-2-bromobenzylamine (50.0 mg/kg, sc) and 5,7-dihydroxytryptamine (5,7-DHT) (37.5 microg icv, half in each lateral ventricle), respectively, were administered toWistar rats on the first and third days of postnatal ontogeny, and dopamine (DA) agonist-induced behaviors were assessed in adulthood. At eight weeks, using an HPLC/ED technique, DSP-4 treatment was associated with a reduction in NE content of the corpus striatum (> 60%), hippocampus (95%), and frontal cortex (> 85%), while 5,7-DHT was associated with an 80-90% serotonin reduction in the same brain regions. DA content was unaltered in the striatum and the cortex. In the group lesioned with both DSP-4 and 5,7-DHT, quinpirole-induced (DA D(2) agonist) yawning, 7-hydroxy-DPAT-induced (DA D(3) agonist) yawning, and apomorphine-induced (non-selective DA agonist) stereotypies were enhanced. However, SKF 38393-induced (DA D(1) agonist) oral activity was reduced in the DSP-4 + 5,7-DHT group. These findings demonstrate that DA D(2)- and D(3)-agonist-induced behaviors are enhanced while DA D(1)-agonist-induced behaviors are suppressed in adult rats in which brain noradrenergic and serotoninergic innervation of the brain has largely been destroyed. This study indicates that noradrenergic and serotoninergic neurons have a great impact on the development of DA receptor reactivity (sensitivity).
authors.affiliation: Department of Pharmacology, Medical University of Silesia, Zabrze, Poland. pnowak@sum.edu.pl
authors.forename: Przemysław
authors.initials: P
authors.lastname: Nowak
authors.forename: Dariusz
authors.initials: D
authors.lastname: Nitka
authors.forename: Adam
authors.initials: A
authors.lastname: Kwieciński
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Jośko
authors.forename: Jacek
authors.initials: J
authors.lastname: Drab
authors.forename: Dorota
authors.initials: D
authors.lastname: Pojda-Wilczek
authors.forename: Jacek
authors.initials: J
authors.lastname: Kasperski
authors.forename: Richard M
authors.initials: RM
authors.lastname: Kostrzewa
authors.forename: Ryszard
authors.initials: R
authors.lastname: Brus
mesh_terms: D015116:5,7-Dihydroxytryptamine / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D001596:Benzylamines / Q000633:toxicity*; D018491:Dopamine Agonists / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000502:physiology; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000502:physiology; D012701:Serotonin / Q000502:physiology
chemical_list: D001596:Benzylamines; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; C012102:DSP 4; D009638:Norepinephrine