Only repeated administration of the serotonergic agonist 8-OH-DPAT improves place lerning of rats subjected to fimbria-fornix transection

TY - JOUR

T1 - Only repeated administration of the serotonergic agonist 8-OH-DPAT improves place lerning of rats subjected to fimbria-fornix transection

AU - Rytter, Hana Malá

AU - Arnberg, Kasper

AU - Chu, David

AU - Kjær Nedergaard, Signe

AU - Witmer, Jacqlyn

AU - Mogensen, Jesper

PY - 2013

Y1 - 2013

N2 - Serotonergic agonists may act neuroprotectively against brain injury. This study addressed the therapeutic potential of 8-hydroxy-2-di-n-propylamino- tetralin (8-OH-DPAT), a selective 5-HT1A/7 receptor agonist, after mechanical brain injury, and evaluated its effects in terms of acquisition of an allocentric place learning task in a water maze. Rats were divided into 6 experimental groups, three of which were subjected to bilateral transection of fimbria-fornix (FF), while three groups were given control surgery (Sham). After surgery, within both the lesioned, and sham-operated animals, respectively, one group was administered a single dose of saline, one group was given a single dose (0.5 mg/kg/b.w.) of 8-OH-DPAT, and one group was treated with daily administration of 8-OH-DPAT (0.5 mg/kg/b.w.) for eight days. The acquisition of the water maze based place learning task started on the 8th day post-surgery and continued for 20 days. The results show that the lesioned group subjected to repeated administration of 8-OH-DPAT demonstrated a significantly improved acquisition of the place learning task compared to the vehicle injected lesion group. In contrast, the lesioned group treated with a single administration displayed impaired performance compared to the baseline lesion group. There were no significant effects of the 8-OH-DPAT administration in the sham control groups. We conclude that only the repeated stimulation of the 5-HT 1A/7 system was associated with beneficial, recovery enhancing effects.

AB - Serotonergic agonists may act neuroprotectively against brain injury. This study addressed the therapeutic potential of 8-hydroxy-2-di-n-propylamino- tetralin (8-OH-DPAT), a selective 5-HT1A/7 receptor agonist, after mechanical brain injury, and evaluated its effects in terms of acquisition of an allocentric place learning task in a water maze. Rats were divided into 6 experimental groups, three of which were subjected to bilateral transection of fimbria-fornix (FF), while three groups were given control surgery (Sham). After surgery, within both the lesioned, and sham-operated animals, respectively, one group was administered a single dose of saline, one group was given a single dose (0.5 mg/kg/b.w.) of 8-OH-DPAT, and one group was treated with daily administration of 8-OH-DPAT (0.5 mg/kg/b.w.) for eight days. The acquisition of the water maze based place learning task started on the 8th day post-surgery and continued for 20 days. The results show that the lesioned group subjected to repeated administration of 8-OH-DPAT demonstrated a significantly improved acquisition of the place learning task compared to the vehicle injected lesion group. In contrast, the lesioned group treated with a single administration displayed impaired performance compared to the baseline lesion group. There were no significant effects of the 8-OH-DPAT administration in the sham control groups. We conclude that only the repeated stimulation of the 5-HT 1A/7 system was associated with beneficial, recovery enhancing effects.

KW - Faculty of Social Sciences

KW - 5-HT

KW - Serotonin

KW - Hjerneskade

KW - Hippocampus

KW - Fimbria-fornix

KW - 8-OH-DPAT

KW - place learning

KW - Rotte

KW - Dyremodel

KW - rehabilitering

KW - Funktionel genopretning

KW - agonist

KW - Cognition

KW - Indlæring

KW - Hukommelse

KW - Problemløsning

KW - Plasticitet

KW - Neural plasticitet

U2 - 10.1016/j.pbb.2013.05.008

DO - 10.1016/j.pbb.2013.05.008

M3 - Journal article

C2 - 23680575

SN - 0091-3057

VL - 109

SP - 50

EP - 58

JO - Pharmacology Biochemistry and Behavior

JF - Pharmacology Biochemistry and Behavior

ER -