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Dose-dependent effects of buspirone on behavior and cerebral glucose metabolism in rats

Freo, Ulderico and Pietrini, Pietro and Pizzolato, Gilberto and Furey, Maura L. and Merico, Antonio and Ruggero, Susanna and Dam, Mauro and Battistin, Leontino Dose-dependent effects of buspirone on behavior and cerebral glucose metabolism in rats. Brain Research, 677 (2). 213 - 220. ISSN 0006-8993 (1995)

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In this study we compared the effects of the anxiolytic buspirone on behavior and regional cerebral metabolic rates for glucose (rCMRglc) with those of the reference serotonin (5-HT)1A agonist 8-hydroxy-2(di-N-propylamino)tetralin (DPAT). Behavioral effects were assessed by scoring the 5-HT syndrome. rCMRglc was measured in 56 brain regions by using the quantitative autoradiographic 14C2-deoxyglucose technique, at 10 min after i.p. injection of \{DPAT\} (1 mg/kg) or buspirone (0.4, 4 and 40 mg/kg) in awake male Fischer-344 rats. Whereas \{DPAT\} produced an intense 5-HT syndrome, buspirone had no behavioral effect. A low dose (0.4 mg/kg) of buspirone reduced rCMRglc in 18 brain areas (32%), more markedly in limbic areas and raphe nuclei. These were the only rCMRglc effects buspirone had in common with the potent 5-HT1A agonist \{DPAT\} and suggest that low dose buspirone activates preferentially 5-HT1A receptors. Hence, this receptor subtype may mediate buspirone functional effects on the limbic system and, given the role of these brain areas in mood control, possibly buspirone therapeutic actions. High doses (4 and 40 mg/kg) of buspirone produced widespread rCMRglc decreases in 46 (82%) and 44 (79%) of the areas studied and increased rCMRglc in one brain area, the lateral habenula, that was not affected by \{DPAT\} or a low dose of buspirone. The topographic distribution and direction of rCMRglc changes by high doses of buspirone differ from those produced by the 5-HT1A agonist DPAT. Instead these changes resemble the rCMRglc effects of dopaminergic \{D2\} antagonists like haloperidol and are consistent with some pharmacological and binding properties of buspirone. In summary, this study suggests that buspirone produces dual, dose-dependent rCMRglc effects: (i) at a low dose rCMRglc reductions in limbic areas and raphe nuclei, probably due to preferential activation of 5-HT1A receptors, and (ii) at higher doses widespread rCMRglc reductions along with a rCMRglc increase in the lateral habenula resulting from dopamine \{D2\} receptor blockade.

Item Type: Article
Identification Number: 10.1016/0006-8993(95)00140-L
Uncontrolled Keywords: Buspirone; rCMRglc; Serotonin 5-HT; DPAT; Anxiolytic
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Research Area: Computer Science and Applications
Depositing User: Caterina Tangheroni
Date Deposited: 04 Apr 2016 08:32
Last Modified: 05 Apr 2016 08:11
URI: http://eprints.imtlucca.it/id/eprint/3344

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