title: Serotoninergics attenuate hyperlocomotor activity in rats. Potential new therapeutic strategy for hyperactivity.
abstract: Hyperactivity is thought to be associated with an alteration of dopamine (DA) neurochemistry in brain. This conventional view became solidified on the basis of observed hyperactivity in DA-lesioned animals and effectiveness of the dopaminomimetics such amphetamine (AMP) in abating hyperactivity in humans and in animal models of hyperactivity. However, because AMP releases serotonin (5-HT) as well as DA, we investigated the potential role of 5-HT in an animal model of hyperactivity. We found that a greater intensity of hyperactivity was produced in rats when both DA and 5-HT neurons were damaged at appropriate times in ontogeny. Therefore, previously we proposed this as an animal model of attention deficit hyperactivity disorder (ADHD) - induced by destruction of dopaminergic neurons with 6-hydroxydopamine (6-OHDA) (neonatally) and serotoninergic neurons with 5,7-dihydroxytryptamine (5,7-DHT) (in adulthood). In this model effects similar to that of AMP (attenuation of hyperlocomotion) were produced by m-chlorophenylpiperazine (m-CPP) but not by 1-phenylbiguanide (1-PG), respective 5-HT2 and 5-HT3 agonists. The effect of m-CPP was shown to be replicated by desipramine, and was largely attenuated by the 5-HT2 antagonist mianserin. These findings implicate 5-HT neurochemistry as potentially important therapeutic targets for treating human hyperactivity and possibly childhood ADHD.
authors.affiliation: Department of Pharmacology, Medical University of Silesia, 41-808 Zabrze, Poland.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Brus
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Nowak
authors.forename: Ryszard
authors.initials: R
authors.lastname: Szkilnik
authors.forename: Urszula
authors.initials: U
authors.lastname: Mikolajun
authors.forename: Richard M
authors.initials: RM
authors.lastname: Kostrzewa
mesh_terms: D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D005260:Female; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D016627:Oxidopamine; D011247:Pregnancy; D011595:Psychomotor Agitation / Q000378:metabolism* / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D018759:Adrenergic Uptake Inhibitors; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D016627:Oxidopamine