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J P Herman

Publications and source records attributed to J P Herman.

At least 55 records · Page 3Linked to original sources
PubMed1996

Immunoautoradiographic and in situ hybridization analysis of corticotropin-releasing hormone biosynthesis in the hypothalamic paraventricular nucleus.

Corticotropin-releasing hormone (CRH) gene transcription and mRNA expression are keyed to stimuli activating the pituitary-adrenocortical axis, suggesting a connection between neuronal activation and synthesis of active peptide. However, the relationship between CRH mRNA and levels of CRH peptide remains to be definitively established. The present report characterizes an immunoautoradiographic (IAR) strategy to assess CRH peptide expression in an anatomical context. Non-fixed tissue sections through the rat hypothalamus were reacted with a primary antibody against rat CRH, followed by incubation with [35S] or [125I] labeled secondary antibody. Autoradiography performed on reacted sections revealed that CRH immunoreactivity could be detected in CRH-containing regions of the hypothalamus and amygdala. Generation of CRH signal was blocked by preabsorption of primary antibody with CRH peptide, demonstrating antibody specificity. IAR performed on nitrocellulose blotted with synthetic CRH peptide revealed a linear relationship between peptide quantity and intensity of autoradiographic signal, verifying that this method is appropriate for semi-quantitative analysis of CRH peptide regulation. Assessment of CRH peptide regulation revealed a significant increase in CRH content in adrenalectomized rats (ADX) relative to sham-adrenalectomized (SHAM) controls (196%). In situ hybridization performed on adjacent sections revealed a similar increase in CRH mRNA expression in ADX rats (256%), and a significant correlation between CRH peptide and mRNA measures (r = 0.68). No ADX induced changes were seen in median eminence, dorsomedial hypothalamus or central amygdaloid nucleus. The results of this study indicate that CRH biosynthesis appears to be driven by amount of available mRNA, rather than changes in translational efficacy. In addition, the IAR technique appears ideally suited to allow concomitant assessment of mRNA and protein expression within defined populations of CNS neurons.

Adrenalectomy↗
PubMed1996

Expression and glucocorticoid regulation of natriuretic peptide clearance receptor (NPR-C) mRNA in rat brain and choroid plexus.

The natriuretic peptide clearance receptor (NPR-C) binds atrial natriuretic peptide, brain natriuretic peptide and C-type natriuretic peptide with high affinity. This receptor lacks an intracellular guanylate cyclase domain, and is believed to exert biological actions by sequestration of released natriuretic peptides and/or inhibition of adenylate cyclase. The present report summarizes the first detailed mapping of NPR-C mRNA in rat brain. In situ hybridization analysis revealed high levels of NPR-C mRNA expression in frontal and retrosplenial granular cortices, medial preoptic nucleus, ventral cochlear nucleus and choroid plexus. NPR-C mRNA expression was also observed in deep layers of neocortex and limbic cortex, posterior cortical amygdala, ventral subiculum, amygdalohippocampal area, and dentate gyrus. Positive hybridization signal was observed in both anterior and intermediate lobes of the pituitary gland. Regulatory studies indicated that expression of NPR-C mRNA was increased in the medial preoptic nucleus of adrenalectomized rats, suggesting negative glucocorticoid regulation. No changes in NPR-C mRNA expression were observed in frontal cortex or choroid plexus. These results suggest a role for the NPR-C in modulation of natriuretic peptide availability and/or adenylate cyclase activity in a subset of central natriuretic peptide circuits concerned with cortical, olfactory and neuroendocrine functions. Response of the NPR-C gene to changes in circulating hormones suggests the capacity for glucocorticoid modulation of natriuretic peptide action at the receptor level.

Adrenalectomy↗
PubMed1996

Phenotype of striatal cells expressing c-Fos following amphetamine treatment of rats with intrastriatal dopaminergic grafts.

Activation of the nigrostriatal dopaminergic system by psychostimulants such as amphetamine increases c-Fos expression in the striatum, mostly in the striatonigral substance P-ergic pathway. This effect is greatly reduced in the neostriatum deprived of dopaminergic afferents. Dopaminergic grafts implanted into the denervated neostriatum restore the reactivity of the striatum to amphetamine. However, the number of striatal neurons expressing c-Fos is greatly increased in the graft-bearing striatum compared with the normal striatum. We examined whether this increase in the number of c-Fos-expressing neurons corresponds to the recruitment of a new neuron population, or whether it reflects an increase in the proportion of substance P-ergic neurons exhibiting activation of c-Fos. Adult rats received a unilateral 6-hydroxydopamine lesion of the ascending dopaminergic mesotelencephalic pathway, and a suspension of embryonic mesencephalic neurons was subsequently implanted into the denervated neostriatum. Three months after implantation, animals were injected with d-amphetamine (5 mg/kg) and killed 2 h later. In the first experiment, striatal sections were processed to visualize both c-Fos protein, by immunohistochemistry, and preproenkephalin A or substance P, by in situ hybridization. In the second experiment, c-Fos and neuropeptide Y were visualized on the same sections. In addition, some sections incubated with anti-c-Fos antibody were counterstained with toluidine blue in order to determine whether cholinergic neurons were expressing c-Fos following amphetamine treatment. The density of neurons expressing c-Fos following amphetamine treatment was three-fold higher in the graft-bearing striata than in the striata of control animals. Approximately 75% of the c-Fos expressing cells were substance P-ergic in control animals whereas 6% were enkephalinergic and only a few were neuropeptide Y-ergic or cholinergic. Similar proportions were found in the graft-bearing striatum, signifying that the pattern of activation of c-fos following amphetamine administration is not changed by the graft. Thus, the increased expression of c-Fos predominantly reflects a graft-induced increase in the proportion of neurons expressing c-Fos within the same population of neurons which normally expresses c-Fos in the striatum, i.e. the striatonigral substance P-ergic neurons; there is no recruitment of a new neuronal population. This increased activation of the striatonigral substance P-ergic pathway may underlie the abnormal behavioural reactions brought about by amphetamine-induced stimulation of the implanted dopaminergic neurons.

Amphetamine↗
PubMed1996

Neuronal circuit regulation of the hypothalamo-pituitary-adrenocortical stress axis.

The hypothalamo-pituitary-adrenocortical (HPA) axis is the primary modulator of the adrenal glucocorticoid stress response. Activation of this axis occurs by way of a discrete set of neurons in the hypothalamic paraventricular nucleus (PVN). The PVN neuron appears to be affected by multiple sources, including (1) brainstem aminergic/peptidergic afferents; (2) blood-borne information; (3) indirect input from limbic system-associated regions, including the prefrontal cortex, hippocampus, and amygdala; and (4) local-circuit interactions with the preoptic-hypothalamic continuum. Analysis of the literature suggests that different classes of stressor employ different stress circuits. Severe physiologic ("systemic") stress appears to trigger brainstem/circumventricular organ systems that project directly to the paraventricular nucleus. In contrast, stressors requiring interpretation with respect to previous experience ("processive" stressors) reach the PVN by way of multisynaptic limbic pathways. Limbic regions mediating processive stress responses appear to have bisynaptic connections with the PVN, forming intervening connections with preoptic/hypothalamic GABAergic neurons. Stressors of the latter category may thus require interaction with homeostatic information prior to promoting an HPA response. The HPA stress response thus appears to be a product of both the physiologic importance of the stimulus and the specific pathways a given stimulus excites.

Adrenocorticotropic Hormone↗
PubMed1995

In situ hybridization analysis of vasopressin gene transcription in the paraventricular and supraoptic nuclei of the rat: regulation by stress and glucocorticoids.

Hypothalamic arginine vasopressin-containing neurons are prime elements in central circuits regulating the hypothalamo-pituitary-adrenocortical stress response. It is known that release and synthesis of vasopressin are cued by stressful stimuli. The present study was designed to assess effects of stress on vasopressin transcription and mRNA expression in defined populations of vasopressin neurons in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Intron- and exon-directed in situ hybridization analyses were used to examine stress regulation of vasopressin heteronuclear (hn) gene transcription and mRNA levels. Actions of glucocorticoids on vasopressin induction were tested using adrenalectomized rats implanted with subcutaneous pellets delivering a constant, physiological dose of corticosterone. Pellet implantation into adrenalectomized rats allows for normal pituitary-adrenal tone in the absence of the ability to mount glucocorticoid stress responses. Elevation of vasopressin heteronuclear (hn) RNA in the medial parvicellular PVN was observed in both normal and adrenalectomized-corticosterone replaced rats as early as 30 minutes after stress initiation. In control rats, vasopressin hnRNA levels returned to baseline by 120 minutes. In contrast, vasopressin hnRNA remained elevated 120 minutes post-restraint in adrenalectomized-corticosterone replaced rats, indicating that the glucocorticoid stress response acts to rapidly inhibit vasopressin transcription. Significant changes in post-stress vasopressin mRNA levels were observed in the parvicellular PVN of control rats 90 minutes following restraint induction, returning to normal expression profiles by 120 minutes. Adrenalectomized-replaced rats showed elevated vasopressin mRNA expression at all time points examined. No changes were observed in magnocellular vasopressin-containing nuclei at any time point, suggesting that magnocellular vasopressin is not induced by this particular stress paradigm. Thus, in parvicellular paraventricular nucleus neurons the vasopressin gene is rapidly induced by stress. Restraint-induced up-regulation of vasopressin transcription is limited by glucocorticoid secretion, consistent with direct actions of glucocorticoid negative feedback on the vasopressin gene in parvicellular neurons.

Animals↗
PubMed1995

Distribution of natriuretic peptide precursor mRNAs in the rat brain.

Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) represent members of a recently discovered neuropeptide family involved in central regulation of endocrine and autonomic functions. The present study employed an in situ hybridization approach to provide the first detailed comparative mapping of ANP, BNP, and CNP mRNAs in brain. Results indicate that ANP mRNA is highly expressed in anterior olfactory nuclei, limbic cortices, dorsal endopiriform nucleus, hippocampal subfield CA1, cortical amygdaloid nuclei, medial habenula, anteroventral periventricular and arcuate nuclei, periventricular stratum, zona incerta, mammillary nuclei, inferior olive, nucleus ambiguus, and pontine paragigantocellular nuclei. CNP mRNA is expressed at highest levels in olfactory nuclei, limbic cortices, dorsal endopiriform nucleus, hippocampal subfields CA1-3, anteroventral periventricular and arcuate nuclei, and numerous brainstem regions (including the pontine, lateral reticular, solitary tract, prepositus hypoglossal, and spinal trigeminal nuclei). Positive labeling for BNP mRNA was not observed in brain. The presence of both ANP and CNP mRNA in the same regions of distinct nuclei (e.g., the anteroventral periventricular and arcuate nuclei) suggests the potential for coexpression. Overall, the present data are consistent with a prominent role for both ANP and CNP in neuroendocrine regulation and central cardiovascular integration. The extensive localization of ANP and/or CNP mRNA in olfactory nuclei, limbic cortex, hippocampus, amygdala and diencephalic limbic relays further indicate a putative role for ANP and CNP as neuromodulators of olfactory/limbic information processing.

Animals↗
PubMed1995

Stress regulation of mineralocorticoid receptor heteronuclear RNA in rat hippocampus.

Localization and regulation of mineralocorticoid receptor (MR) heteronuclear RNA (hnRNA) was assessed in rat hippocampus using an intron-directed in situ hybridization approach. The presence of hnRNA in the cell nucleus reflects recent gene transcriptional events and can be used as an index of neuronal transcriptional activation or inhibition. In the present study, sections incubated with an MR intron probe labeled cells in all regions known to contain MR mRNA. Signal generated by the intron probe was localized specifically to the nuclear compartment, consistent with recognition of hnRNA. Analysis of distribution across hippocampus indicated that MR hnRNA was particularly abundant in dentate gyrus (DG). In contrast, MR mRNA shows similar levels of expression across all hippocampal subfields. Exposure of animals to acute restraint markedly reduced MR hnRNA levels in CA1 and DG 60 min and 120 min following stress exposure, consistent with reduced gene transcription. These data support the hypothesis that stress-induced glucocorticoid secretion can rapidly affect transcription of steroid receptor genes. MR mRNA levels did not decrease over comparable time periods, suggesting either a significant lag-time between transcriptional changes and changes in cytoplasmic mRNA pools or stimulus-driven alterations in post-transcriptional RNA processing.

Animals↗
PubMed1995

The neonatal lesion of the meso-telencephalic dopaminergic pathway increases intrastriatal D2 receptor levels and synthesis and this effect is reversed by neonatal dopaminergic rich-graft.

The ascending dopaminergic pathway of 3-day-old rats has been unilaterally destroyed by the injection of 6-hydroxydopamine into the lateral hypothalamus. Five days later, a suspension containing embryonic dopaminergic neurones was injected in the lesioned neostriatum. Rotational responses to dopaminergic agonists were tested eight months after grafting and animals were killed one month later. Neostriatal dopaminergic D1 and D2 receptors were examined using autoradiography while changes in D2 receptor mRNA levels were studied by in situ hybridization. The lesion induced a behavioural hypersensitivity - as manifested in contralateral rotations - to dopaminergic D1 (SKF 38393) or D2 (LY 171555) agonists which was abolished by the graft. Density of D1 receptors was not affected by the lesion while D2 receptors density was increased by 20-25% in the more rostral part of the neostriatum. Changes in D2 mRNA after the lesion paralleled those observed for D2 receptor density, i.e. D2 mRNA level was increased by 15-19% in the rostral neostriatum. The graft did not influence D1 receptor densities but reversed the post-lesion increase of D2 receptors associated parameters. It is concluded that dopaminergic grafts implanted in neonatal hosts are able to normalise the density of D2 receptors by an action on their synthesis.

Animals↗
PubMed1995

Increased expression of 5HT2 receptor mRNA in rat striatum following 6-OHDA lesions of the adult nigrostriatal pathway.

Neonatal destruction of the dopaminergic nigrostriatal system with the specific neurotoxin 6-hydroxydopamine (6-OHDA) leads to increases in several components of the adult serotonergic raphe-striatal system. Although results following similar lesions of adult ventral midbrain dopaminergic neurons are less consistent, increases in striatal serotonin (5-hydroxytryptamine; 5HT) fiber density, content, and metabolites have been reported. The effect of such lesions upon gene expression for striatal 5HT receptors, however, has not been determined. The purpose of the present study was to investigate possible changes in expression of several 5HT receptor mRNAs in rat striatum following destruction of the adult nigrostriatal pathway. In situ hybridization for 5HT1A, 5HT1C, and 5HT2 receptor subtype mRNAs was performed in rat striatum following unilateral injection of 6-OHDA into the medial forebrain bundle or directly into the ventral midbrain. Compared to the uninjected control side, a significant increase in the hybridization density for 5HT2 receptor mRNA was observed in the caudate-putamen ipsilateral to the 6-OHDA lesion (P < 0.05). In contrast, no significant changes in the hybridization densities for 5HT1A or 5HT1C receptor mRNAs were detected. The observed increase in striatal 5HT2 receptor mRNA levels after the dopamine-depleting lesion provides evidence for plasticity of the serotonergic raphe-striatal system in the adult rat at the level of striatal gene expression. Furthermore, the present data indicate that dopaminergic mechanisms differentially regulate the expression of 5HT receptor mRNAs in adult rat striatum.

Animals↗
PubMed1995

Pattern and time course of immediate early gene expression in rat brain following acute stress.

The pattern and time course of brain activation in response to acute swim and restraint stress were examined in the rat by in situ hybridization using complementary RNA probes specific for transcripts encoding the products of the immediate early genes c-fos, c-jun and zif/268. A widespread pattern of c-fos messenger RNA expression was detected in response to these stressors; surprisingly, the expression patterns were substantially similar following both swim and restraint stress. A dramatic induction of c-fos messenger RNA was observed in numerous neo- and allocortical regions, the lateral septal nucleus, the hypothalamic paraventricular and dorsomedial nuclei, the anterior hypothalamic area, the lateral portion of the retrochiasmatic area, the medial and cortical amygdaloid nuclei, the periaqueductal gray, and the locus coeruleus; however, a prominent induction of c-fos was also seen in numerous additional subcortical and brainstem regions. Although not as widely expressed in response to stress as c-fos, induction of zif/268 messenger RNA was also detected throughout many brain areas; these regions were largely similar to those in which c-fos was induced, although in a number of regions zif/268 was expressed in regions devoid of c-fos messenger RNA. Few brain areas showed increased expression of c-jun following stress; these regions also showed induction of c-fos and/or zif/268. The time courses of expression of all three immediate early genes were similar, with peak levels observed at the 30 or 60 min time point, and a markedly reduced signal evident at 120 min post-stress. However, in a number of cases a delayed and/or prolonged induction was noted that may be indicative of secondary neuronal activation. A number of recent studies have attempted to define neural pathways which convey stress-related information to the hypothalamic-pituitary-adrenal axis. The present results reveal a widespread pattern of neuronal activation in response to acute swim or restraint stress. These findings may aid in the identification of stress-specific neural circuits and are thus likely to have important implications for our understanding of neuronal regulation of the stress response.

Animals↗
PubMed1995

The C-type natriuretic peptide receptor is the predominant natriuretic peptide receptor mRNA expressed in rat hypothalamus.

The natriuretic peptide receptors (NPR) are membrane-bound guanylate cyclases with extracellular binding domains specific for particular members of the natriuretic peptide family. NPR-A binds atrial natriuretic peptide (ANP) with high affinity, whereas the NPR-B appears to be specific for C-type natriuretic peptide (CNP). Previous data indicating extensive overlap between localization of ANP and CNP in hypothalamic neuroendocrine circuits suggest the importance of determining whether specificity of natriuretic peptide action may be conferred via receptor type present on target cells. To address this issue, we used in situ hybridization histochemistry to localize NPR-A and NPR-B mRNA in the hypothalamus. NPR-A mRNA was not found in substantial abundance in any hypothalamic nucleus; however, detectable NPR-A signal was observed in other brain regions, including the subfornical organ and medial habenula. In contrast, NPR-B mRNA was expressed throughout the hypothalamus, including neurons of the magnocellular and parvocellular paraventricular, the arcuate, and the supraoptic nuclei. Expression was also seen in other nuclei essential to neuroendocrine control, including the median preoptic, anteroventral periventricular, tuberomammilary, ventromedial and suprachiasmatic nuclei. NPR-B mRNA was also observed in the neural lobe of the pituitary gland, suggesting expression by pituicytes. The results suggest that NPR-B is the primary natriuretic peptide receptor in hypothalamus, and by inference indicate that CNP is the primary active natriuretic peptide in neuroendocrine regulation.

Animals↗
PubMed1995

Contribution of the ventral subiculum to inhibitory regulation of the hypothalamo-pituitary-adrenocortical axis.

Anatomical studies indicate that the ventral subiculum is in a prime position to mediate hippocampal inhibition of the hypothalamo-pituitary-adrenocortical (HPA) axis. The present study evaluated this hypothesis by assessing HPA function following ibotenic acid lesion of the ventral subiculum region. Rats with lesions of the ventral subiculum (vSUB) or ventral hippocampus (vHIPPO) did not show changes in basal corticosterone (CORT) secretion at either circadian peak or nadir time points when compared to sham-lesion rats (SHAM) or unoperated controls. However, rats with vSUB lesions exhibited a prolonged glucocorticoid stress response relative to all other groups. Baseline CRH mRNA levels were significantly increased in the medial parvocellular paraventricular nucleus (PVN) of the vSUB group relative to controls. CRH mRNA differences were particularly pronounced at caudal levels of the nucleus, suggesting topographic organization of vSUB interactions with PVN neurons. Notably, the vHIPPO group, which received large lesions of ventral CA1, CA3 and dentate gyrus without significant subicular damage, showed no change in stress-induced CORT secretion, suggesting that the ventral subiculum proper is principally responsible for ventral hippocampal actions on the HPA stress response. No differences in medial parvocellular PVN AVP mRNA expression were seen in either the vSUB or vHIPPO groups. The results indicate a specific inhibitory action of the ventral subiculum on HPA activation. The increase in CRH biosynthesis and stress-induced CORT secretion in the absence of changes in baseline CORT secretion or AVP mRNA expression suggests that the inhibitory actions of ventral subicular neurons affect the response capacity of the HPA axis.

Adrenal Cortex↗
PubMed1995

Regulatory changes in neuroendocrine stress-integrative circuitry produced by a variable stress paradigm.

Stress represents a complex stimulus to neuroendocrine systems regulating homeostasis. By and large, stress effects are mediated by stress-integrative corticotropin-releasing hormone (CRH) neurons present in the medial parvocellular division of the hypothalamic paraventricular nucleus (PVN). These neurons summate a large variety of neuronal and hormonal signals to eventually yield a physiologically meaningful level of circulating glucocorticoids. In the present experiments, we examined the effects of a chronic variable-stressor paradigm on indices of adrenocorticotropic hormone (ACTH) secretagogue biosynthesis in the PVN and adrenocorticosteroid receptor mRNA expression in the hippocampal formation, PVN and cortex. The variable-stressor paradigm produces a syndrome consistent with chronic stress, including baseline hypersecretion of corticosterone, ACTH and prolactin, and adrenal hypertrophy. CRH mRNA levels in the PVN are increased some 61%, consistent with the observed hypothalamo-pituitary-adrenal (HPA) up-regulation. There was a small but significant increase in arginine vasopressin (AVP) mRNA expression in individual parvocellular PVN neurons (16%), and no demonstrable increase in the number of AVP mRNA-containing neurons. No change in AVP expression was seen in the magnocellular PVN, supraoptic or suprachiasmatic nuclei. In all, these data highlight the importance of CRH in maintaining HPA up-regulation in the face of prolonged challenge. To investigate effects of chronic stress on the regulation of glucocorticoid receptivity, mineralocorticoid receptor (MR) and glucocorticoid receptor mRNA expression was assessed in the hippocampus, frontoparietal cortex and PVN. Chronic stress significantly down-regulated MR mRNA expression in subfields CA1, CA3 and the dentate gyrus (DG), and GR mRNA expression in subfields CA1, the DG and frontoparietal cortex. The reduction in receptor biosynthesis suggests the capacity for stress to modulate the impact of glucocorticoid on hippocampal cell physiology at the genomic level, potentially influencing processes ranging from cognition to feedback regulation of the HPA axis. At the level of the parvocellular PVN, GR mRNA expression was decreased to 60% of control values. GR mRNA expression was negatively correlated with PVN CRH mRNA expression, suggesting a relationship between elevated CRH gene expression and down-regulation of GR at the level of the PVN.

Adrenocorticotropic Hormone↗
PubMed1995

Lamina-specific expression of adhesion molecules in developing chick optic tectum.

The optic tectum is the major synaptic target of retinal axons in birds. In the chick, retinal ganglion cell axons enter the optic tectum through a superficial lamina (the stratum opticum), extended branches into deeper laminae, and arborize in specific "retinorecipient" laminae, where they form synapses. Studies using an organotypic culture system have provided evidence that the tectum bears a series of distinct, lamina-specific, cell surface-associated cues that direct these axonal behaviors (Yamagata and Sanes, 1995). Here, we have used a panel of antibodies to 30 membrane and matrix components to ask whether known adhesive molecules are distributed in lamina-specific patterns. Among many spatiotemporal pattern of expression documented, three were particularly noteworthy: (1) The cell adhesion molecules NgCAM/L1 and TAG-1/axonin-1 were concentrated in the stratum opticum. (2) SC1/JC7/DM-GRASP/BEN, N-cadherin, neuropilin, polysialylated N-CAM, and glycoconjugates recognized by the lectin VVA-B4 were concentrated in retinorecipient laminae. (3) Neurofascin, tenascin-C/cytotactin, and a matrix molecule defined by the "Sigma" antibody were present at highest levels in areas that border the retinorecipient laminae. Some members of each group (NgCAM/L1, TAG-1/axonin, SC1/JC7, polysialic acid, VVA-B4-receptors, and neurofascin) appeared on schedule and in lamina-restricted patterns in tecta from embryos that had been enucleated before retinal axons left the eye. Thus, molecules in these three categories could provide signals to retinal axons that promote extension through the stratum opticum, induce arborization or synaptogenesis in retinorecipient laminae, and prevent sprouting into adjoining laminae. Interestingly, N-cadherin accumulated in retinorecipient laminae only following the onset of synapse formation, and failed to accumulate in enucleated tecta. Immunoelectron microscopy of normal tecta demonstrated the presence of N-cadherin in the synaptic cleft, suggesting a role for this molecule in synaptic maintenance.

Animals↗
PubMed1994

The increase in striatal neuropeptide Y immunoreactivity induced by neonatal dopamine-depleting lesions in rats is reversed by intrastriatal dopamine-rich transplants.

The aim of the present experiment was to test whether: (i) the destruction of the dopaminergic meso-telencephalic pathway in neonatal rats induces an increase in the density of Neuropeptide Y immunoreactive (NPY-IR) neuronal perikarya within the denervated neostriatum; (ii) embryonic dopaminergic neurons grafted into the neonatal neostriatum could block such an effect of the lesion. As a control, density of NPY-IR neurones was also examined in rats lesioned and/or grafted at adulthood. The ascending dopaminergic system of 3-day-old rat pups or adult rats was unilaterally lesioned by intrahypothalamic injection of 6-hydroxydopamine. Grafting was performed six days later. The neonatal lesion increased the number of NPY-IR neurones on the lesioned side by 24% as compared to the contralateral neonstriatum. This increase was abolished in the neostriatum bearing dopaminergic grafts as evaluated six weeks after grafting. These effects are similar to that observed in animals lesioned and/or grafted as adults and further extend the range of post-lesion modifications which can be reversed by the implantation of embryonic DA neurones to neonates.

Amphetamine↗