Serotoninergics Attenuate Hyperlocomotor Activity in Rats. Potential New Therapeutic Strategy for Hyperactivity
Document Type
Article
Publication Date
12-1-2004
Description
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 as amphetamine (AMP) in abating hyperactivity in humans and in animal models of hyperactivity. However, because AMPreleases 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.
Citation Information
Brus, Ryszard; Nowak, Przemyslaw; Szkilnik, Ryszard; Mikolajun, Urszula; and Kostrzewa, Richard M.. 2004. Serotoninergics Attenuate Hyperlocomotor Activity in Rats. Potential New Therapeutic Strategy for Hyperactivity. Neurotoxicity Research. Vol.6(4). 317-325. https://doi.org/10.1007/BF03033442 PMID: 15545015 ISSN: 1029-8428