Activation and blockade of serotonin6receptors in the dorsal hippocampus enhance T maze and hole-board performance in a unilateral 6-hydroxydopamine rat model of Parkinson's disease.
The role of dorsal hippocampus (DH) serotonin6(5-HT6) receptors in memory is unknown, particularly in memory impairment of Parkinson's disease. We tested here effects of activation and blockade of DH 5-HT6receptors on working and hippocampus-dependent memories in rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. The lesion induced working and hippocampus-dependent memory impairments as measured by the T-maze rewarded alternation and hole-board tests, and decreased dopamine (DA) levels in the striatum, medial prefrontal cortex (mPFC), DH and amygdala. Intra-DH injection of 5-HT6receptor agonist WAY208466 (1.5, 3 and 6µg/rat) did not change choice accuracy and the number of head-dippings when re-exposure to hole-board in sham-operated rats, while 5-HT6receptor antagonist SB258585 (4µg/rat) increased choice accuracy and decreased the number of head-dippings. In the lesioned rats, both WAY208466 (3 and 6µg/rat) and SB258585 (2 and 4µg/rat) increased choice accuracy and decreased the number of head-dippings. Neurochemical results showed that intra-DH injection of WAY208466 or SB258585 produced significant effects on DA and noradrenaline (NA) levels in the mPFC (WAY208466: sham-operated, NA -44%; lesioned, DA 522%, NA -47%; SB258585: sham-operated, DA 72%, NA 85%; lesioned, DA -68%), DH (WAY208466: lesioned, DA 427%; SB258585: sham-operated, DA 119%, NA 206%) and amygdala (WAY208466: sham-operated, NA -28%; lesioned, DA 302%; SB258585: sham-operated, NA 183%); however, 5-HT levels in these brain regions were not changed. These findings suggest DA depletion plays a key role in working and hippocampus-dependent memory impairments, and 5-HT6receptors in the DH are involved in the regulation of the memories.
Department of Clinical Medicine, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
Kun Cheng
KC
Liu
Department of Clinical Medicine, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
Jun Yi
JY
Li
Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
Wen
W
Xie
Department of Rehabilitation Medicine, the Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China.
Li Bo
LB
Li
Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
Jin
J
Zhang
Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
Cheng Xue
CX
Du
Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
Yu Ming
YM
Zhang
Department of Rehabilitation Medicine, the Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China.
Hui Hui
HH
Tan
Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
Hui Sheng
HS
Wang
Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: zhangli1998@mail.xjtu.edu.cn.
Li
L
Zhang
D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004195:Disease Models, Animal; D004298:Dopamine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects*; D008570:Memory, Short-Term / Q000187:drug effects*; D017072:Neostriatum / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease; D020734:Parkinsonian Disorders; D017397:Prefrontal Cortex / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism* / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology
D011985:Receptors, Serotonin; C097216:serotonin 6 receptor; D012701:Serotonin; D016627:Oxidopamine; D004298:Dopamine; D009638:Norepinephrine
5-HT(6) receptors; Dorsal hippocampus; Memory; Parkinson's disease; Rat