Serotoninergics attenuate hyperlocomotor activity in rats. Potential new therapeutic strategy for hyperactivity.
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.
Brus
Ryszard
R
Department of Pharmacology, Medical University of Silesia, 41-808 Zabrze, Poland.
Nowak
Przemyslaw
P
Szkilnik
Ryszard
R
Mikolajun
Urszula
U
Kostrzewa
Richard M
RM
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
D018759:Adrenergic Uptake Inhibitors; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D016627:Oxidopamine