Activation and blockade of serotonin 6 receptors in the dorsal hippocampus enhance T maze and hole-board performance in a unilateral 6-hydroxydopamine rat model of Parkinson's disease

• Published in: Brain research Vol. 1650; p. 184
• Main Authors: Liu, Kun Cheng, Li, Jun Yi, Xie, Wen, Li, Li Bo, Zhang, Jin, Du, Cheng Xue, Zhang, Yu Ming, Tan, Hui Hui, Wang, Hui Sheng, Zhang, Li
• Format: Journal Article
• Language: English
• Published: Netherlands 01.11.2016
• Subjects: Amygdala - drug effects; Amygdala - physiology; Animals; Disease Models, Animal; Dopamine - pharmacology; Hippocampus - drug effects; Male; Memory - drug effects; Memory, Short-Term - drug effects; Neostriatum - drug effects; Norepinephrine - pharmacology; Oxidopamine - pharmacology; Parkinson Disease; Parkinsonian Disorders; Prefrontal Cortex - drug effects; Rats; Rats, Sprague-Dawley; Receptors, Serotonin - metabolism; Receptors, Serotonin - physiology; Serotonin - pharmacology; Parkinson's disease; Rat; Memory; 5-HT receptors; Dorsal hippocampus
• ISSN: 1872-6240

The role of dorsal hippocampus (DH) serotonin (5-HT ) receptors in memory is unknown, particularly in memory impairment of Parkinson's disease. We tested here effects of activation and blockade of DH 5-HT receptors 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-HT receptor 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-HT receptor 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-HT receptors in the DH are involved in the regulation of the memories.