Serotonin receptor subtype gene expression in the hippocampus of aged rats following chronic amitriptyline treatment.
The raphe-hippocampal 5-HT system plays a key role in the modulation of mood, memory and neuroendocrine responses. In the elderly, there is an increased incidence of disturbances of these functions. We examined the effects of ageing and of chronic antidepressant treatment upon 5-HT receptor subtype mRNA expression in the hippocampus and raphe of cognitively tested rats. Amitriptyline treatment decreased 5-HT1A receptor mRNA expression in the dorsal raphe nucleus of the aged rats (24% fall compared to saline treated controls, p<0.01) but not in the young rats. Neither age nor amitriptyline (10 mg/kg, i.p.) administration for 10 weeks altered 5-HT1A, 5-HT2A, 5-HT2C or 5-HT7 receptor mRNA expression in any hippocampal subregion. This suggests a difference in responsiveness to amitriptyline with ageing originating at the level of the raphe 5-HT1A autoreceptor gene expression.
Centre for the Study of the Ageing Brain, Molecular Medicine Centre, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK. jy@srv0.med.ed.ac.uk
J L
JL
Yau
T
T
Olsson
J
J
Noble
J R
JR
Seckl
D000375:Aging / Q000378:metabolism*; D017398:Alternative Splicing; D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D004027:Diencephalon / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D017403:In Situ Hybridization; D008297:Male; D009474:Neurons / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000235:genetics*; D044263:Receptors, Serotonin, 5-HT1; D014158:Transcription, Genetic / Q000187:drug effects*
D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; C104425:serotonin 7 receptor; D000639:Amitriptyline