5-HT1A and 5-HT2A receptor effects on recognition memory, motor/exploratory behaviors, emotionality and regional dopamine transporter binding in the rat
Journal
Behavioural Brain Research
Series/Report No.
Behavioural Brain Research
Journal Volume
469
Start Page
115051
ISSN
0166-4328
Date Issued
2024-07
Author(s)
Nikolaus, Susanne
Henke, Jan
Beu, Markus
Fazari, Benedetta
Almeida, Filipe Rodrigues
Abdel-Hafiz, Laila
Antke, Christina
Hautzel, Hubertus
Mamlins, Eduards
Müller, Hans-Wilhelm
Huston, Joseph P.
von Gall, Charlotte
Giesel, Frederik L.
Abstract
Both dopamine (DA) and serotonin (5-HT) play key roles in numerous functions including motor control, stress response and learning. So far, there is scarce or conflicting evidence about the effects of 5-HT1A and 5-HT2A receptor (R) agonists and antagonists on recognition memory in the rat. This also holds for their effect on cerebral DA as well as 5-HT release. In the present study, we assessed the effects of the 5-HTR agonist 8-OH-DPAT and antagonist WAY100,635 and the 5-HTR agonist DOI and antagonist altanserin (ALT) on rat behaviors. Moreover, we investigated their impact on monoamine efflux by measuring monoamine transporter binding in various regions of the rat brain. After injection of either 8-OH-DPAT (3 mg/kg), WAY100,635 (0.4 mg/kg), DOI (0.1 mg/kg), ALT (1 mg/kg) or the respective vehicle (saline, DMSO), rats underwent an object and place recognition memory test in the open field. Upon the assessment of object exploration, motor/exploratory parameters and feces excretion, rats were administered the monoamine transporter radioligand N-o-fluoropropyl-2b-carbomethoxy-3b-(4-[I]iodophenyl)-nortropane ([I]-FP-CIT; 8.9 ± 2.6 MBq) into the tail vein. Regional radioactivity accumulations in the rat brain were determined post mortem. Compared vehicle, administration of 8-OH-DPAT impaired memory for place, decreased rearing behavior, and increased ambulation as well as head-shoulder movements. DOI administration led to a reduction in rearing behavior but an increase in head-shoulder motility relative to vehicle. Feces excretion was diminished after ALT relative to vehicle. Dopamine transporter (DAT) binding was increased in the caudateputamen (CP), but decreased in the nucleus accumbens (NAC) after 8-OH-DPAT relative to vehicle. Moreover, DAT binding was decreased in the NAC after ALT relative to vehicle. Findings indicate that 5-HTR inhibition and 5-HTR activation may impair memory for place. Furthermore, results imply associations not only between recognition memory, motor/exploratory behavior and emotionality but also between the respective parameters and the levels of available DA in CP and NAC.
Subjects
5-HT(1A) receptor
5-HT(2A) receptor
Dopamine transporter binding
Emotionality
Object and place recognition
Publisher
Elsevier BV
Type
journal article