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Serotoninergics attenuate hyperlocomotor activity in rats. Potential new therapeutic strategy for hyperactivity

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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 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 bym-chlorophenylpiperazine (m-CPP) but not by 1-phenylbiguanide (1-PG), respective 5-HT2 and 5-HT3 agonists. The effect ofm-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.

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  1. Department of Pharmacology, Medical University of Silesia, 41-808, Zabrze, Poland

    Ryszard Brus, Przemyslaw Nowak, Ryszard Szkilnik & Urszula Mikolajun

  2. Department of Pharmacology, Quillen College of Medicine, East Tennessee State University, PO Box 70577, 37614, Johnson City, TN, USA

    Richard M. Kostrzewa

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  1. Ryszard Brus
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Brus, R., Nowak, P., Szkilnik, R. et al. Serotoninergics attenuate hyperlocomotor activity in rats. Potential new therapeutic strategy for hyperactivity. neurotox res 6, 317–325 (2004). https://doi.org/10.1007/BF03033442

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