Neonatal maternally deprived rats have as adults elevated basal pituitary-adrenal activity and enhanced susceptibility to apomorphine.
Maternal deprivation of neonatal rats for 24 h enhances the adrenocortical response to stress and/or adrenocorticotropin hormone (ACTH) stimulation during the stress hyporesponsive period (SHRP). The present study tests the hypothesis that such maternally deprived neonatal male rats show altered hypothalamic-pituitary-adrenal (HPA) regulation not only immediately after deprivation but also in later life. In addition, we found previously that neonatal changes in HPA activity preceded modulation of nigrostriatal dopamine function. Therefore, we also measured dopamine responsiveness in adult rats which were deprived of their mother during infancy. Neonatal male rats were maternally deprived for 24 h at the age of 3 days, whereas rats of the control group were left undisturbed. At 60 days of age deprived and non-deprived rats were decapitated and brain, adrenal glands and thymus were removed. Trunk blood was collected for determination of plasma ACTH, corticosterone and prolactin concentrations using radioimmunoassay procedures. mRNA levels of mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs), corticotropin-releasing hormone (CRH) mRNA and tyrosine hydroxylase (TH) mRNA were measured in brain sections with in situ hybridization. In a second group of male deprived and non-deprived rats apomorphine-induced stereotypic gnawing behaviour was examined at 60 days of age as a measure for functional activity of the dopamine system. Deprived neonatal rats showed the following characteristics as compared with non-deprived rats: (i) lower basal CRH mRNA concentration in parvocellular neurons of the paraventricular nucleus of the hypothalamus (PVN), while basal plasma ACTH and corticosterone concentrations were significantly elevated. Basal prolactin levels were not different. (ii) Similar hippocampal MR and GR mRNA levels. (iii) Significantly reduced GR mRNA levels in PVN and anterior pituitary. (iv) Significantly enhanced apomorphine-induced stereotypic gnawing behaviour and (v) higher TH mRNA levels in substantia nigra, while no changes were found in the ventral tegmental area (VTA). It is concluded that maternally deprived neonatal male rats display as young adults elevated basal pituitary-adrenal activity and enhanced apomorphine susceptibility.
Rots
N Y
NY
Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, University of Leiden, The Netherlands.
de Jong
J
J
Workel
J O
JO
Levine
S
S
Cools
A R
AR
De Kloet
E R
ER
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001058:Apomorphine / Q000494:pharmacology*; D004351:Drug Resistance; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D008297:Male; D008426:Maternal Deprivation; D010913:Pituitary-Adrenal System / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011987:Receptors, Steroid / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
D012333:RNA, Messenger; D011987:Receptors, Steroid; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine