Maternal separation alters serotonergic transporter densities and serotonergic 1A receptors in rat brain.
BACKGROUND
The basic mechanisms underlying the association between early life maternal separation and adulthood psychiatric disorders are largely unknown. One possible candidate is the central serotonergic system, which is also abnormal in psychiatric illnesses. Neuroadaptational changes in serotonergic transporter and serotonergic 1A receptors may underlie links between early life stress and adulthood psychiatric disorders.


OBJECTIVE
The aim of this study was to investigate the consequences of a rat model of maternal separation on serotonergic transporter and serotonergic 1A receptor densities and function in adult rat forebrain.


METHODS
Rat pups were separated from dams from postnatal day 2 to postnatal day 14, each day, for zero time, 15 min and 180 min to determine the time-course of effects. A non-handled group was added to control for the effects of handling by an experimenter compared with the animal facility-reared group. Quantitative [(125)I]3beta-(4-iodophenyl)tropan-2beta-carboxylic acid methyl ester and [(125)I]-mPPI autoradiography was used to determine serotonergic transporter and serotonergic 1A densities, respectively. Adult rats were challenged with saline or serotonergic 1A agonist (+) 8-hydroxy-2-(di-n-propylamino)tetralin, 0.4 mg/kg, s.c.) and plasma adrenocorticotropic hormone and corticosterone were determined.


RESULTS
serotonergic transporter and serotonergic 1A densities were significantly lower in the non-handled group in the paraventricular, arcuate, dorsomedial and ventromedial nuclei of the hypothalamus. The non-handled group also displayed lower serotonergic transporter and serotonergic 1A densities in the basolateral anterior, basolateral ventral and basomedial amygdaloid nuclei. Serotonergic transporter densities were also decreased in the CA3 area of the hippocampus in the non-handled group. In contrast, the maternal separation 15 min group displayed the highest serotonergic transporter and serotonergic 1A densities in the basomedial nucleus of amygdala, basolateral anterior nucleus of amygdala, basolateral ventral nucleus of amygdala and basomedial nucleus of amygdala amygdaloid nuclei.


CONCLUSIONS
Early life maternal separation and the extent of handling can alter adult brain serotonergic transporter and serotonergic 1A levels and function in the forebrain. Alterations in these serotonergic systems by early rearing conditions might increase vulnerability for behavioral disorders in adulthood.
The Yerkes National Primate Research Center of Emory University, 954 North Gatewood Road, Atlanta, GA 30329, USA. avicen2@emory.edu
A
A
Vicentic
D
D
Francis
M
M
Moffett
A
A
Lakatos
G
G
Rogge
G W
GW
Hubert
J
J
Harley
M J
MJ
Kuhar
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001345:Autoradiography / Q000379:methods; D001522:Behavior, Animal; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D002352:Carrier Proteins / Q000097:blood; D003042:Cocaine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D008426:Maternal Deprivation; D010879:Piperazines / Q000493:pharmacokinetics; D011247:Pregnancy; D011725:Pyridines / Q000493:pharmacokinetics; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D020318:Rats, Long-Evans; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
C416045:4-iodo-N-(2-(4-(methoxyphenyl)-1-piperazinyl)ethyl)-N-2-pyridinylbenzamide; D002352:Carrier Proteins; D007457:Iodine Radioisotopes; D010879:Piperazines; D011725:Pyridines; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000324:Adrenocorticotropic Hormone; D003042:Cocaine