Treatment In Adulthood Research Articles

Trophic Action of Leptin on Hypothalamic Neurons That Regulate Feeding

In adult mammals, the adipocyte-derived hormone leptin acts on the brain to reduce food intake by regulating the activity of neurons in the arcuate nucleus of the hypothalamus (ARH). Here, we report that neural projection pathways from the ARH are permanently disrupted in leptin-deficient (Lepob/Lepob) mice and leptin treatment in adulthood does not reverse these neuroanatomical defects. However, treatment of Lepob/Lepob neonates with exogenous leptin rescues the development of ARH projections, and leptin promotes neurite outgrowth from ARH neurons in vitro. These results suggest that leptin plays a neurotrophic role during the development of the hypothalamus and that this activity is restricted to a neonatal critical period that precedes leptin's acute regulation of food intake in adults.

Physical repercussions of childhood-onset growth hormone (GH) deficiency and hGH treatment in adulthood.

The aim of this study was to evaluate the physical condition of young adults with childhood-onset growth hormone deficiency (GHD) before and after 6 months of hGH therapy. Ten men and three women, aged 22.3 +/- 3.3 years, previously treated with hGH for 8.6 +/- 4.07 years at a dose of 0.5 IU/kg/week with a minimun of 2.5 years without treatment at the time of study, were studied. Nine patients presented isolated GHD and four patients had combined pituitary hormone deficiencies; they were treated with hGH at a dosage of 0.125 IU/kg/week for the first month and 0.25 IU/kg/week for the following 5 months. The tests performed were: exercise test, heart rate, rating of perceived exertion, blood lactate analysis, jump test and hand grip. Body composition was also analyzed using Holtain Body Analysis. Skinfold thickness was measured at four sites (triceps, biceps, subscapular and suprailiac). After 6 months of treatment a significant increase in lean body mass (42.0 +/- 7.72 to 46.2 +/- 8.01 kg, p = 0.004) and decrease in fat mass (19.6 +/- 10.01 to 16.1 +/- 10.79 kg, p = 0.01) were observed. The initial physical condition of these patients was lower than expected, and improved after treatment with an increase in maximum oxygen consumption from 2.0 +/- 1.2 to 2.33 +/- 0.68 l x min(-1) (p = 0.01). Maximum heart rate increased significantly from 189 +/- 14.8 to 193 +/- 11.7 beats x min(-1) (p = 0.03). No modifications were observed in anaerobic threshold (4 mmol x l(-1)). Only slight, non-significant increases were observed in jump and strength tests. We conclude that a) adults with childhood-onset growth hormone deficiency present a deficient physical condition and lower than expected for age and sex; b) this condition improves after 6 months of treatment, particularly in the aerobic aspect; c) changes observed in strength tests were discrete and of little significance; and d) the increase observed in lean body mass plays an important role in these changes. Further studies investigating GH action on maximum oxygen consumption are required, once its basic mechanism of action has been determined, either in the heart or peripheral factors.

Bone mineral density in adult patients with Turner's syndrome: analyses of the effectiveness of GH and ovarian steroid hormone replacement therapies.

To analyze the effects of treatments with GH and cyclic estrogen/progesterone (E/P) replacement on bone mineralization in patients with Turner's syndrome (TS), bone mineral density (BMD) was measured longitudinally. BMDs of the whole body and the lumbar spine in 16 adult female patients with TS (17-38 year old; 0-20 years by length of E/P treatment) were assessed using dual energy X-ray absorptiometry one to 5 times over a treatment period of up to 7 years maximum. GH treatment was performed in 9 cases (GH group), but not in the remaining 7 (non-GH group). E/P replacement therapy was initiated in all patients after they finished GH administration. The BMDs of both the whole body and the lumbar spine in the patients with TS were significantly less than those in age-matched normal subjects, and did not improve with E/P treatment. Although there were no differences in final body height and age at the beginning of E/P administration between the GH and non-GH groups, whole body BMD in the GH group was significantly lower than that in the non-GH group. These results indicate that GH administration in childhood and adolescence and E/P treatment in adulthood did not increase bone mineralization in the TS patients. Therefore, we can conclude that the optimal protocol of hormonal replacement therapy with GH and E/P during childhood and adolescence should be established as soon as possible.

The Aromatase Knock-Out Mouse Provides New Evidence That Estradiol Is Required during Development in the Female for the Expression of Sociosexual Behaviors in Adulthood

We used estrogen-deficient aromatase knock-out (ArKO) mice to determine whether estrogens contribute to the development of the brain and behavior in females. Female mice of three different genotypes [i.e., wild type (WT), heterozygous (HET), and homozygous (ArKO)] were ovariectomized in adulthood and subsequently tested for odor preferences (choice: intact male vs estrous female) in a Y-maze. When treated with testosterone, ArKO females spent significantly less time sniffing odors (both volatile and nonvolatile) from either male or female stimuli compared with WT and HET females. When given direct access to anesthetized stimulus animals or when given a choice between odor and visual cues from both stimulus animals, ArKO females continued to spend less time investigating the stimuli compared with WT and HET females. These defects in olfactory investigation of ArKO females were partially corrected with estradiol treatment in adulthood. Estradiol-treated ArKO females no longer differed from WT and HET females in the time spent investigating either nonvolatile odors or the anogenital region of anesthetized animals. However, ArKO females still investigated volatile odors and/or visual cues less than WT and HET females. Sexual receptivity was severely impaired in ArKO females after treatments with estradiol and progesterone that successfully induced receptivity in WT and HET females. Furthermore, ArKO females showed diminished levels of male sexual behaviors, whereas WT and HET females readily mounted an estrous female. Together, these findings demonstrate that estrogen is required for normal female development. The concept that the female brain develops in the absence of any hormonal stimulation should therefore be reconsidered.

Childhood trauma has dose-effect relationship with dropping out from psychotherapeutic treatment for bulimia nervosa: a replication.

The primary goal of this study was to replicate the finding that experiences of childhood trauma have a dose-effect relationship with dropping out from psychotherapeutic treatment for bulimia nervosa. It also aimed to replicate logistic regression findings that parental break-up predicts dropping out. The cohort consisted of 114 women consecutively presenting to an outpatient eating disorders clinic with bulimia nervosa or atypical bulimia nervosa. Data were gathered using a retrospective, case-note approach and were analysed using logistic regression (LR). A correlation technique was employed to assess the presence of a dose-effect relationship between experiences of trauma in childhood and dropping out. LR models were double cross-validated between this and an earlier cohort. The dose-effect relationship between experiences of childhood trauma and dropping out was confirmed. Witnessing parental break-up in childhood again predicted dropping out of treatment in adulthood. Cross-validation of LR equations was unsuccessful. These results strongly suggest that experiences of childhood trauma have a dose-effect relationship with dropping out. Parental break-up is a stable predictor of dropping out. It is possible that these experiences influence attachment style, particularly the ability to make and maintain a trusting relationship with a psychotherapist. Clinical implications are discussed.

Neuronal Size in the Spinal Nucleus of the Bulbocavernosus: Direct Modulation by Androgen in Rats with Mosaic Androgen Insensitivity

The motoneurons of the spinal nucleus of the bulbocavernosus (SNB) and its target muscles, the bulbocavernosus and levator ani, form a sexually dimorphic circuit that is developmentally dependent on androgen exposure and exhibits numerous structural and functional changes in response to androgen exposure in adulthood. Castration of male adult rats causes shrinkage of SNB somata, and testosterone replacement reverses this effect, but the site at which androgen is acting to cause this change is undetermined. We exploited the X-chromosome residency of the androgen receptor (AR) gene to generate androgenized female rats that were heterozygous for the testicular feminization mutant (tfm) AR mutation and that, as a consequence of ontogenetic random X-inactivation, expressed a blend of androgen-sensitive wild-type cells and tfm-affected androgen-insensitive cells in the SNB. Chronic testosterone treatment of adult mosaics increased soma sizes only in androgen-competent wild-type SNB cells. The size of tfm-affected SNB somata in the same animals did not differ from the size of either the wild-type or tfm-affected SNB neurons in control mosaics that did not receive androgen treatment in adulthood. Because the muscle targets of the SNB are known to be uniformly androgen-sensitive in tfm mosaics, this mosaic analysis provides unambiguous evidence that androgenic effects on motoneuron soma size are mediated locally in the SNB. It is possible that the neuronal AR plays a permissive role in coordinating the actions of androgen.

Phenotypical segregation among female rat hypothalamic gonadotropin-releasing hormone neurons as revealed by the sexually dimorphic coexpression of cholecystokinin and neurotensin

The neuroendocrine control of the gonad is exerted primarily by the gonadotropin-releasing hormone neurons located in the septum and the hypothalamus. Despite their sexually dimorphic activity, tonic in males and phasic in females, these neurons have not appeared qualitatively different between sexes in intrinsic organization or chemical phenotype. Here, by using multiple-label immunocytochemistry, it is demonstrated that the phenotype of gonadotropin-releasing hormone neurons is sex specific. In females only, 54.5% of them co-expressed cholecystokinin immunoreactivity and 29.4% additionally expressed neurotensin immunoreactivity. These multipeptidergic neurons were observed in the hypothalamus but not in the septum. During postnatal development, cholecystokinin and neurotensin immunoreactivities were first detected in gonadotropin-releasing hormone-containing axons of the median eminence at vaginal opening, suggesting an involvement of the neuropeptides in peri-ovulatory events. This peptidergic phenotype was not apparent in females ovariectomized as adults but was reinstated by estradiol treatment. In adult males, the testicle does not control this phenotype because orchidectomized adults did not display it, whatever the post-operative delay (one to five weeks) or substitutive chronic steroid treatment (testosterone or estradiol). The testicle may, however, masculinize the phenotype neonatally because estradiol or testosterone treatment in adulthood induced an expression of cholecystokinin immunoreactivity in gonadotropin-releasing hormone-containing axons of the median eminence in both males and females that were gonadectomized at birth. This procedure, however, failed to significantly induce an expression of neurotensin immunoreactivity, suggesting a role of the postnatal ovary on this element of the chemistry of gonadotropin-releasing hormone neurons. Thus, the gonad permanently organizes the gonadotropin-releasing hormone neuronal population, resulting, at least in females, in a mosaic of phenotypically distinct, functional subunits.

Effect of Long-Term Castration and Long-Term Androgen Treatment on Sexually Dimorphic Estrogen-Inducible Progesterone Receptor mRNA Levels in the Ventromedial Hypothalamus of Whiptail Lizards

In whiptail lizards, as in laboratory rodents, females will respond to exogenous estrogen by increasing progesterone receptor (PR) or PR mRNA in the ventromedial hypothalamus (VMH) while males show an attenuated response to the same treatment. In rodents, neonatal hormone manipulations affect the adult expression of this trait; however, few investigators have examined the effects of hormone treatment in adulthood. Therefore the current study was carried out to determine whether observed sex differences in the estrogen response in adulthood may be modified by steroid hormone manipulation. We castrated male whiptail lizards for 1 week (short term) or 6 weeks (long term). We also gonadectomized female whiptails and implanted them with either a Silastic capsule containing testosterone or an empty capsule. At the end of that time all implants were removed and the animals were injected with either estradiol benzoate (EB) or steroid suspension vehicle and their brains were assayed for PR mRNA expression usingin situhybridization. The results demonstrate that in male whiptail lizards, long-term castration increases sensitivity to estradiol as measured by induction of PR mRNA in the VMH; EB-injected long-term castrated males were not different from EB-injected females. However, long-term androgenization did not attenuate the estrogen response in females. This suggests that attenuation of the estrogen response in males requires activation by testicular secretions, but that females cannot be made to show a male phenotype via testosterone administration.

NGF prevents further atrophy of cholinergic cells of the nucleus basalis due to cortical infarction in adult post-hypothyroid rats but does not restore cell size compared to euthroid rats

We have tested the hypotheses that nerve growth factor treatment in adult post-hypothyroid rats can: (1) restore cross-sectional area of cholinergic cells of the nucleus basalis and (2) prevent further atrophy of these neurons following cortical infaction. In addition, we assessed the expression of p75 NGFR and p140 trkA mRNAs in the nucleus basalis cells of post-hypothyroid rats. Rats were rendered hypothyroid by the addition of propylthiouracil to their diet beginning on embryonic day 19 until the age of 1 month. At this time both the pups and their dams continued to receive 0.05% propylthiouracil in their diet and the pups were thyroidectomized. At 60 days, propylthiouracil treatment was interrupted and thyroxine levels were restored to normal by daily subcutaneous administration of physiological levels of thyroxine. Morphometric analysis identified atrophied nucleus basalis magnocellularis cholinergic cells at two ages, days 75 and 105, identified by in situ hybridization for p75 NGFR and p140 trkA mRNAs in methylene blue stained cells (day 75) and choline acetyltransferase immunostaining (day 105). The mean number of silver grains (pixels) per μm 2 (mean±S.E.M.) of cell body cross-sectional area for p75 NGFR mRNA in the nucleus basalis magnocellularis of euthyroid rats was 3.43±0.89, which was not statistically different from post-hypothyroid animals (4.02±1.07). A similar finding was noted for p140 trkA mRNA: mean number of grains in the euthyroid group was 5.54±0.96 and was not statistically different from the post-hypothyroid group (6.32±1.45). Nerve growth factor treatment in adulthood (between days 75 and 82) did not restore cross-sectional area from early thyroid deprivation. However, it prevented further atrophy of nucleus basalis magnocellularis neurons following cortical devascularization inflicted in adulthood (day 75).

Programming of brainstem serotonin transporter development by prenatal glucocorticoids

Prenatal stress or exposure to excess glucocorticoids are known to alter central nervous system function and to result in lasting changes in reactions to stress. The potential involvement of specific elements of brainstem serotonergic neurons was examined in the current study. Pregnant rats were given 0.05, 0.2 or 0.8 mg/kg of dexamethasone on gestational days 17, 18 and 19, and the effects on development of the serotonin presynaptic transporter were assessed from birth to young adulthood by measurement of [ 3H]paroxetine binding to membrane preparations. Dexamethasone produced a dose-dependent retardation of body and brainstem growth but evoked a significant elevation of [ 3H]paroxetine binding that persisted into adulthood. Effects on [ 3H]paroxetine binding were robust even at the lowest dose, which did not suppress growth, indicating that the programming of this transporter is more sensitive to glucocorticoids than is general development. At the highest dose, promotional effects on serotonin transporter expression were offset by impaired growth, so that the peak effect was seen at the intermediate dose of dexamethasone. There were no comparable effects on serotonin transmitter levels, indicating selectivity toward promotion of transporter expression as distinct from simply increasing the number of serotonergic persistent than those on other monoamine transporters, and is not shared by postnatal treatment or by treatment in adulthood, it likely represents specific programming by glucocorticoids during the prenatal period. Aberrant serotonergic transporter expression may contribute to alterations of synaptic function that ultimately produce the physiological abnormalities seen after prenatal stress or glucocorticoid treatment.

Effects of prenatal morphine and adult estrogen administration on mu-opioid inhibition of norepinephrine release from hypothalamic slices.

The present study tested the hypotheses that exposure to morphine in utero (10 mg/kg twice a day on gestation days 11-18) and acute estrogen treatment in adulthood alter mu-opioid regulation of hypothalamic norepinephrine (NE) release in sexually mature rats. Both basal and KCl-stimulated NE releases were measured in superfused hypothalamic and preoptic area (POA) slices preloaded with 3H-NE. The mu-opioid receptor agonist D-Ala2, MePhe4-Gly-ol5-enkephalin (DAMGO; 10 or 100 nM) or the opioid antagonist naloxone (1 microM) was applied to some slices 15 min prior to KCl stimulation. Prenatal morphine had no effect on basal or KCl-stimulated release of preloaded 3H-NE from hypothalamic and POA slices from adult male progeny. Neither the mu-opioid agonist DAMGO nor the nonspecific antagonist naloxone significantly affected KCl-evoked overflow of 3H-NE in slices from either brain region of male rats. Adult female offspring were ovariectomized (OVX), and some were injected with a replacement dose of estrogen 48 h prior to sacrifice. Prenatal morphine had no effect on basal or KCl-stimulated release of 3H-NE from hypothalamic or POA slices or on the response of slices to opioid drugs. Estrogen treatment modestly increased KCl-evoked release of 3H-NE from POA slices from females. Moreover, there was a significant interaction between opioid drugs and estrogen treatment on KCl-evoked overflow of 3H-NE. In hypothalamic and POA slices from OVX females, DAMGO reduced KCl-evoked efflux of 3H-NE. This inhibitory effect of DAMGO was not apparent in slices from estrogen-treated females. In addition, naloxone increased KCl-stimulated NE release in slices from both hypothalamus and POA of estrogen-treated female rats but not control OVX females. Thus, prenatal exposure to morphine does not alter basal, KCl-evoked or mu-opioid modulation of NE efflux from hypothalamic or POA slices in adult progeny of either sex. However, treatment of adult, OVX females with estrogen attenuates mu-opioid inhibition and promotes the appearance of naloxone facilitation of KCl-evoked 3H-NE release from hypothalamic and POA slices.

Effect of prenatal allylestrenol treatment (hormonal imprinting) on the serum testosterone and progesterone level in adult rats

1. 1. Female rats were treated with allylestrenol on the 15th, 17th and 19th days of their pregnancy. 2. 2. Serum testosterone and progesterone level of their three months old offspring were higher than control in males and females, respectively. 3. 3. Serum progesterone levels of females, treated both prenatally and in adulthood, does not differ from control values. Serum testosterone level of males, treated prenatally and in adulthood, is lower than control. 4. 4. One single allylestrenol treatment in adulthood does not make changes in testosterone concentration in males, but progesterone level is elevated in females. 5. 5. Our experiments draw attention to the dangers of prenatal allylestrenol treatments (administered in case of endangered pregnancies) which may have long lasting effects on sexual steroid hormone levels.

Effect of neonatal allylestrenol treatment (hormonal imprinting) on the serum testosterone and progesterone concentration in adult rat.

Serum testosterone concentration was significantly elevated in adult male rats by a single perinatal allylestrenol administration. One week after a second allylestrenol treatment in adulthood the hormone concentration dropped below the control values. Serum progesterone concentration was significantly lowered in adult female rats by a single perinatal allylestrenol administration. Following a second allylestrenol treatment in adulthood the hormone concentration reached the control values. These experiments demonstrate that the hormonal imprinting caused by allylestrenol (a steroid used in the treatment of endangered pregnancy) not only acts at receptor level and produces changes in sexual behaviour, but also induces modifications in serum hormone concentrations.

Benzpyrene treatment in adulthood increases the testosterone level in neonatally steroid(allylestrenol)-treated male rats

1. 1. Serum testosterone level was significantly elevated in adult male rats after a single perinatal allylestrenol administration. 2. 2. Benzpyrene treatment of adult rats perinatally treated with allylestrenol, did not cause changes 1 week after benzpyrene treatment, but 3 weeks later an extremely high serum testosterone level was found. 3. 3. In control animals benzpyrene administration in adulthood did not influence the serum testosterone level either 1 or 3 weeks following the treatment.

P75. Purification of α-2HS-glycoprotein from a human plasma fraction and development of an enzyme linked immunoabsorvent assay

Although there is much evidence for age differences in behavioural responses to psychostimulants in rats, the differential, lasting impact of drug exposures has rarely been investigated using direct comparisons of adolescent and adult rats. Male rats were pre-treated with 0.5 mg/kg amphetamine or saline on either postnatal days (P) 31 and P33 or P76 and P78, and locomotor activity was measured for 1 h. Adolescent, and not adult, rats showed a significant increase in distance traveled from the first to second pre-treatment. There was no evidence of sensitization of locomotor activity in either adolescents or adults on Challenge 1 to the same dose of amphetamine when tested 12 days later on P45 (late adolescence) or on P90. Rats that were pre-treated as adolescents exhibited locomotor sensitization to 1.5 mg/kg amphetamine as adults (P60) on Challenge 2, 27 days after pre-treatment, particularly in the group that had also received amphetamine on Challenge 1 at P45. Rats that were pre-treated as adults did not show sensitization on Challenge 2. The results suggest that the rapid adaptations to drug exposures in adolescence have greater consequences than identical treatment in adulthood, and highlight the unique vulnerability of adolescents to brief, low dose drug exposure.

Effects of Testosterone Propionate upon the Sexual and Aggressive Behavior of Adult Male Marmosets ( Callithrix jacchus) Castrated as Neonates

In New World monkeys of the family Callitrichidae (marmosets and tamarins), females frequently give birth to dizygotic twins. Twins share a placental circulation throughout fetal development and are hemopoietic chimeras. Despite this, there is no masculinization (freemartinism) in females which develop next to a male co-twin. It has been suggested that the organizing effects of testicular androgen upon sexual differentiation of the brain occur mainly during early postnatal development in male callitrichids, rather than in utero. However, this report demonstrates activation of masculine copulatory behavior by testosterone propionate (TP) administered to adult male marmosets ( N = 8) which were castrated in infancy (between Days 1-7). Effects of neonatal castration upon aggressive behavior during pair tests with females (high frequencies of aggression) anti intact adult males (low frequencies of aggression) were also reversed by TP treatment in adulthood. While early postnatal androgen secretion plays an important role in behavioral development in marmosets, it appears that a substantial degree of neural sexual differentiation occurs in utero in males of this callitrichid species.

Early estrogen treatment alone causes female zebra finches to produce learned, male‐like vocalizations

The male zebra finch produces learned song and long calls while the female does not. This difference in behavior is believed to result from the action of sex steroids on brain areas responsible for vocal production and learning. In this study, the female zebra finch was used to explore further the specific role sex steroids play in vocal masculinization. We show that estradiol (E2) treatment at birth was sufficient to masculinize the vocal behavior of female zebra finches. Thirteen of 18 females treated with E2 as nestlings produced song-like vocalizations. Fifteen of 18 produced long calls with male-typical features. The degree of masculinization varied between individuals. Of the 15 early E2 females that produced at least one type of male-like vocalization, 7 showed evidence of vocal learning from their tutors. The ability of E2 to cause masculinization of vocal behavior was age dependent: treatment from birth was most effective, treatment at 20 days of age was partially effective, and treatment in adulthood was ineffective. The effect of subsequent testosterone exposure in adulthood differed depending on the quality of the vocalization produced after E2 treatment alone. These results suggest that E2 may play a more important role than previously thought in the development of sex differences in vocal behavior. Furthermore, this study demonstrates that exogenous E2 treatment alone can induce vocal learning.

Early estrogen treatment of female zebra finches masculinizes the brain pathway for learned vocalizations

Telencephalic nucleus HVC and its two efferent targets, RA and X, play essential roles in the production of complex, learned vocalizations in the male zebra finch. Normal females do not produce these learned vocalizations; HVC, RA, and X are small in volume, and HVC and RA are not synaptically connected. We have shown that estrogen treatment during development causes females to learn and produce male-like vocalizations. This article describes the neural masculinization of these E2 females, replicating and extending the work of others. Female zebra finches were treated with 17 beta-estradiol (E2) at hatching, at 14-22 days of age, or as adults. In adulthood, the volumes of nucleus RA and area X were measured and the efferent projections of nucleus HVC examined using the anterograde tracer PHA-L. Early, sustained E2 treatment caused the greatest increase in the volume of RA and X, the innervation of RA and X by HVC axons, and the masculinization of auditory responses of cells in RA. Treatments that lasted for a shorter period or started later in development resulted in different patterns of partial brain masculinization. E2 treatment in adulthood had no effect on the volume of RA or X or their innervation by HVC. Bilateral lesions of the tracheosyringeal nerves or of HVC had the same effects on the male-typical vocalizations produced by E2 females as they do on the vocalizations produced by males. These results demonstrate that the neural masculinization of telencephalic nuclei induced by E2 treatment sets up a functional circuit in females similar to one in males that enables the learning and production of complex vocalizations.

Dopamine D 1 receptor behavioral responsitivity following selective lesions of the striatal patch compartment during development

The behavioral effects of selective destruction of the dopamine (DA) input to the patch compartment of rat striatum early in development was investigated. Rat pups were given bilateral intrastriatal (i.s.) injections of the neurotoxin 6-hydroxydopamine (6-OHDA) on day of birth (P0) or postnatal day 1 (P1), which resulted in selective behavioral alterations following DA agonist treatment in adulthood. Neonatally-lesioned rats exhibited self-biting behavior following treatment with the DA precursor l-dihydroxyphenylalanine ( l-DOPA). In response to treatment with the selective D 1 agonist SKF38393, there was an increased incidence of abnormal perioral movements. The cataleptogenic effects of the D 1 antagonist SCH23390 and the D 2 antagonist haloperidol were also studied. Neonatally-lesioned rats were significantly less cataleptic compared to control rats following D 1 antagonist treatment, but not following D 2 antagonist treatment. Autoradiographs of [ 3H]mazindol binding to DA uptake sites (a measure of DA terminal density) showed a ‘patchy’ loss of approx. 40–50% in striatal tissue sections derived from the i.s. lesioned rats. These data suggest that injections of 6-OHDA into the striatum during this early postnatal period cause a DA lesion that results in long-term effects on a D 1 receptor system.

Cortical neuron sensitivity to neurotransmitters following neonatal noradrenaline depletion

In order to test the functional significance of rapid eye movement (REM)-sleep and noradrenergic activity for cerebral cortex maturation, rat pups were daily injected with clonidine from 8 to 21 days of life. Previous studies have shown that this treatment reduces the amount of time spent in REM-sleep and the level of noradrenaline turnover in the brain. For long-term consequences of such treatment in adulthood, cortical neuron responses to micro-iontophoretically applied neurotransmitters were studied. No significant differences were found in the single cell responses to glutamate, GABA or noradrenaline in the cerebral cortex of clonidine treated rats as compared with age matched controls. However, the magnitude of GABAergic depression of glutamate induced neuronal responses was greater in the clonidine than in the control group.