Search PubMed⌕ Search

Biomedical subjects

A Pert

Publications and source records attributed to A Pert.

At least 73 records · Page 4Linked to original sources
PubMed1987

Innervation of substantia nigra neurons by cholinergic afferents from pedunculopontine nucleus in the rat: neuroanatomical and electrophysiological evidence.

Dopaminergic neurons of the substantia nigra pars compacta are excited by nicotine and acetylcholine, and possess both high-affinity nicotine binding sites and intense acetylcholinesterase activity, consistent with a cholinoceptive role. A probable source of cholinergic afferents is the pedunculopontine nucleus, which forms part of a prominent group of cholinergic perikarya located caudal to the substantia nigra in the tegmentum. Although pedunculopontine efferents, many of them cholinergic, project to the substantia nigra pars compacta, it has not been established whether they terminate in this structure. In the first experiment, which combined retrograde tracing with immunohistochemical visualization of cholinergic neurons, cholinergic cells in and around the pedunculopontine nucleus were found to send projections to the substantia nigra. This projection was almost completely ipsilateral. Subsequent experiments employed anaesthetized rats; kainate was microinfused into tegmental sites in order to stimulate local cholinergic perikarya, and concurrently, extracellular recordings were made of single dopaminergic neurons in the substantia nigra. Consistent with our anatomical findings, unilateral microinfusion of kainic acid in or near the pedunculopontine nucleus increased the firing rate of dopaminergic neurons situated remotely in the ipsilateral substantia nigra. The kainate-induced excitation of nigral dopaminergic neurons was dose-related and was prevented by intravenous administration of the centrally-acting nicotinic cholinergic antagonist mecamylamine. These results suggest that cholinergic perikarya in the vicinity of the pedunculopontine tegmental nucleus innervate dopaminergic neurons in the substantia nigra pars compacta via nicotinic receptors.

Action Potentials↗
PubMed1986

3H-nicotine and 125I-alpha-bungarotoxin-labeled nicotinic receptors in the interpeduncular nucleus of rats. I. Subnuclear distribution.

The distribution of nicotinic receptors within the interpeduncular nucleus (IPN) was determined in male rats following in vitro labeling with the cholinergic ligands 3H-nicotine and 125I-alpha-bungarotoxin (BTX). Autoradiographic images of two rostrocaudal levels of IPN were analyzed by computer-assisted densitometry and the optical density contributed by displaceable labeling was determined in the rostral, central, intermediate, and lateral subnuclei. 3H-nicotine labeling density within the four subnuclei differs significantly at both levels of IPN. The greatest density of labeling is localized in the rostral subnucleus, followed in order of diminishing density by the central, intermediate, and lateral subnuclei. Labeling within the rostral subnucleus is prominently localized within its central zone. In the central subnucleus, a dense concentration of binding sites is apparent in the middle region, adjacent to less dense vertically oriented columns; 3H-nicotine binding sites in the lateral subnuclei appear to be most concentrated medially, adjacent to the intermediate subnuclei. 125I-BTX labeling density within the four subnuclei also differs significantly at both levels of IPN. The greatest density of labeling is found in the rostral subnucleus, followed in order of decreasing density by the lateral, central, and intermediate subnuclei. The ovoid regions of the rostral subnucleus contain dense 125I-BTX labeling. In the lateral subnuclei, 125I-BTX binding appears to be predominantly along the lateral margins of the subnucleus. The present data indicate that the IPN contains two distinct populations of putative cholinergic nicotinic receptors identified, respectively, by 3H-nicotine and 125I-BTX labeling. Each population of labeled receptors is uniquely localized in patterns that suggest differences in density within and across subnuclei.

Animals↗
PubMed1986

3H-nicotine- and 125I-alpha-bungarotoxin-labeled nicotinic receptors in the interpeduncular nucleus of rats. II. Effects of habenular deafferentation.

The cholinergic innervation of the interpeduncular nucleus (IPN) is wholly extrinsic and is greatly attenuated by bilateral habenular destruction. We describe changes in the labeling of putative nicotinic receptors within this nucleus at 3, 5, or 11 days after bilateral habenular lesions. Adjacent tissue sections of the rat IPN were utilized for 3H-nicotine and 125I-alpha-bungarotoxin (125I-BTX) receptor autoradiography. Compared to sham-operated controls, habenular destruction significantly reduced autoradiographic 3H-nicotine labeling in rostral (-25%), intermediate (-13%), and lateral subnuclei (-36%). Labeling in the central subnucleus was unchanged. Loss of labeling was maximal at the shortest survival time (3 days) and did not change thereafter. In order to establish whether this loss was due to a reduction in the number or the affinity of 3H-nicotine-binding sites, a membrane assay was performed on microdissected IPN tissue from rats that had received surgery 3 days previously. Bilateral habenular lesions produced a 35% reduction of high-affinity 3H-nicotine-binding sites, with no change in binding affinity. Bilateral habenular lesions reduced 125I-BTX labeling in the intermediate subnuclei, and a slight increase occurred in the rostral subnucleus. In the lateral subnuclei, 125I-BTX labeling was significantly reduced (27%) at 3 days but not at later survival times. In view of the known synaptic morphology of the habenulointerpeduncular tract, it is concluded that a subpopulation of 3H-nicotine binding sites within the IPN is located on afferent axons and/or terminals. This subpopulation, located within rostral, intermediate, and lateral subnuclei, may correspond to presynaptic nicotinic cholinergic receptors. Sites that bind 125I-BTX may include a presynaptic subpopulation located in the lateral and possibly the intermediate subnuclei.

Afferent Pathways↗
PubMed1986

CRF-induced seizures and behavior: interaction with amygdala kindling.

Intracerebroventricular (i.c.v.) administration of ovine corticotropin-releasing factor (CRF) in doses varying from 10 to 100 micrograms has been reported to produce the late onset of seizures that resemble those observed during electrical kindling of the amygdala. We assessed the effects of repeated CRF administration on seizure development and on subsequent electrical kindling of the amygdala. Rats were administered vehicle or CRF (100 micrograms in 10 microliter of sterile water, i.c.v.) once daily for 5 consecutive days and were rated for seizures and aggressive behavior. On days 1 or 2, all animals receiving CRF developed major motor seizures of late onset (1-5 h post-injection), accompanied by spiking in the amygdala. By day 5, however, no rats had seizures, suggesting the development of tolerance. Defensive biting attacks were also observed following latencies of several hours and tolerance appeared to develop to these as well. After the CRF regimen, treated rats developed amygdala-kindled seizures following electrical stimulation approximately twice as fast as vehicle-injected controls (P less than 0.03). In a second experiment, rats were electrically kindled or sham-kindled prior to receiving i.c.v. CRF (100 micrograms). Kindled animals were significantly less sensitive to the seizure-inducing effects of CRF (P less than 0.03), but were more intensely aggressive than sham-kindled animals or naive rats receiving CRF for the first time.

Amygdala↗
PubMed1986

In vivo opioid receptor occupation in the rat brain following exercise.

The effects of prolonged swim-stress (2 h and 1 h) upon brain opioid receptor binding of tritiated [3H]diprenorphine were investigated in male Sprague-Dawley rats. This was accomplished by injecting the label intravenously immediately following the swim, then allowing 20 min for tracer washout from non-specific binding sites, sacrificing the animal, dissecting the brain into several discrete areas (medulla-pons, mid-brain, mesolimbic, caudate, thalamus, and hypothalamus), and subsequently preparing homogenates from each brain area. Data were obtained from scintillation counting of the homogenates. A separate support experiment measured circulating beta-endorphin endorphin like immunoreactivity immediately following 2 h of swim-stress. Blood-borne beta-endorphin levels were significantly enhanced by the swim. Additionally, [3H]diprenorphine binding was insignificantly elevated following the 1-h swim and significantly greater in 5 of 6 brain areas examined subsequent to the 2-h swim. Greater availability of opioid receptors to allow enhanced binding of [3H]diprenorphine may have been caused by decreased competition for available receptors from endogenously produced peptides or possibly by alterations in receptor-binding characteristics. These proposed explanations await further investigation. As a result of these studies, we conclude: exercise-induced enhancement of peripheral beta-endorphin probably does not have a supraspinal action; and prolonged swim-stress apparently alters opioid receptor occupancy in the rat brain, and this effect may be dependent upon exercise duration.

Animals↗
PubMed1985

Autoradiographic evidence for nicotine receptors on nigrostriatal and mesolimbic dopaminergic neurons.

Rats received unilateral injections of 6-hydroxydopamine into the medial forebrain bundle, resulting in an ipsilateral loss of striatal dopamine and of dopaminergic perikarya. A concomitant reduction of displaceable tritiated nicotine binding was observed autoradiographically in the ipsilateral substantia nigra, ventral tegmental area, striatum, nucleus accumbens, and olfactory tubercle. Thus, nicotine receptors appear to be located on nigrostriatal and mesolimbic dopaminergic neurons at the level of perikarya and terminals.

Animals↗
PubMed1985

Calcitonin receptors in the rat mesencephalon mediate its analgesic actions: autoradiographic and behavioral analyses.

Autoradiographic analyses of salmon calcitonin (sCT) binding in the rat mesencephalon revealed an exceptionally high concentration of receptors in the ventral and ventrolateral segments of the periaqueductal gray matter (PAG) extending along the entire rostral-caudal axis. Relatively heavy labeling was also seen along a band extending ventrolaterally through the mesencephalic reticular formation. Other receptor-rich areas include the nucleus linearis, pars compacta and lateralis of the substantia nigra, locus coeruleus, parabrachial nuclei and nucleus raphe pontis of the pontine reticular formation. Injections of sCT into the PAG induced a dose-dependent increase in hot-plate latencies. All rostral-caudal levels of these brain regions appeared to be equally responsive. Injections into the midline pontine reticular formation were also effective in increasing response latencies. Unilateral injections into the hypothalamus, medial thalamus, ventral thalamus and mesencephalic reticular formation proved to be ineffective. Human calcitonin (hCT) was considerably less potent. These biological effects are consistent with the potencies of both peptides in displacing 125I-sCT from slide-mounted sections of rat PAG. Naloxone failed to antagonize sCT-induced analgesia, suggesting an opiate independent mechanism for this peptide in eliciting analgesia.

Animals↗
PubMed1985

Comparative localization of neurotensin receptors on nigrostriatal and mesolimbic dopaminergic terminals.

Neurotensin (NT), a brain-gut peptide, possesses many biological actions similar to those reported for neuroleptics. Moreover, it has been shown that NT alters dopaminergic activity of both nigrostriatal and mesolimbic pathways. We now report that NT receptors are located on dopaminergic cell bodies in both systems. However, the proportion of NT receptors on presynaptic dopaminergic terminals appears to be different. NT receptor sites are mainly found on presynaptic dopaminergic terminals in the caudate-putamen while they are pre- and post-synaptically located in the nucleus accumbens and the olfactory tubercule. NT receptors differential localization in these two pathways could be used as a model to study the comparative physiology of various dopaminergic brain systems.

Animals↗
PubMed1985

Electrophysiological actions of nicotine on substantia nigra single units.

Extracellular recordings of single unit activity were made in the substantia nigra (SN) of chloral hydrate-anaesthetized rats. Dopaminergic neurones of the pars compacta (SNC) were stimulated by (-)-nicotine bitartrate (1.0 mg kg-1) given subcutaneously (s.c.). This action was prevented by the secondary amine mecamylamine HCl (2.0 mg kg-1 i.v.) but not by a ganglion-blocking dose of the bisquaternary compound chlorisondamine Cl (0.1 mg kg-1 i.v.). Mecamylamine reduced the spontaneous activity of dopaminergic neurones. Nicotine, when administered intravenously (2-128 micrograms kg-1 cumulative dose), also stimulated dopamine cells and this action was dose-related. Nicotine, administered intravenously, (2-128 micrograms kg-1 cumulative dose) markedly excited non-dopamine cells in the pars reticulata (SNR) in a dose-related manner. In rats pretreated with chlorisondamine (0.1 mg kg-1 i.v.), nicotine induced a small excitatory or depressant action, but the marked excitation was not seen. Mecamylamine (2 mg kg-1 i.v.) completely prevented the actions of nicotine. The results are consistent with a direct excitatory action of nicotine on dopaminergic neurones of the substantia nigra pars compacta. The pronounced excitatory action of systemically administered nicotine on non-dopamine cells of the pars reticulata appears to be of peripheral origin.

Animals↗
PubMed1985

Nicotinic binding in rat brain: autoradiographic comparison of [3H]acetylcholine, [3H]nicotine, and [125I]-alpha-bungarotoxin.

Three radioligands have been commonly used to label putative nicotinic cholinoceptors in the mammalian central nervous system: the agonists [3H]nicotine and [3H]acetylcholine ([3H]ACh--in the presence of atropine to block muscarinic receptors), and the snake venom extract, [125I]-alpha-bungarotoxin([125I]BTX), which acts as a nicotinic antagonist at the neuromuscular junction. Binding studies employing brain homogenates indicate that the regional distributions of both [3H]nicotine and [3H]ACh differ from that of [125I]BTX. The possible relationship between brain sites bound by [3H]nicotine and [3H]ACh has not been examined directly. We have used the technique of autoradiography to produce detailed maps of [3H]nicotine, [3H]ACh, and [125I]BTX labeling; near-adjacent tissue sections were compared at many levels of the rat brain. The maps of high affinity agonist labeling are strikingly concordant, with highest densities in the interpeduncular nucleus, most thalamic nuclei, superior colliculus, medial habenula, presubiculum, cerebral cortex (layers I and III/IV), and the substantia nigra pars compacta/ventral tegmental area. The pattern of [125I]BTX binding is strikingly different, the only notable overlap with agonist binding being the cerebral cortex (layer I) and superior colliculus. [125I]BTX binding is also dense in the inferior colliculus, cerebral cortex (layer VI), hypothalamus, and hippocampus, but is virtually absent in thalamus. Various lines of evidence suggest that the high affinity agonist-binding sites in brain correspond to nicotinic cholinergic receptors similar to those found at autonomic ganglia; BTX-binding sites may also serve as receptors for nicotine and are possibly related to neuromuscular nicotinic cholinoceptors.

Acetylcholine↗
PubMed1984

A mechanism for the analgesic effect of neurotensin as revealed by behavioral and electrophysiological techniques.

Behavioral and electrophysiological techniques were used to examine the effects of local injections of neurotensin (NT) into the periaqueductal gray (PAG). The results of the behavioral experiments showed that injection of NT into the PAG produced dose-dependent analgesia that lasted for as long as 60 min and was not blocked by naloxone. However, electrolytic lesions of the nucleus raphe magnus (NRM) and its surrounding area, abolished the analgesic effect of NT. Electrophysiological experiments indicated that micro-pressure application of NT onto neurons in the PAG had a predominantly excitatory effect. Furthermore, it was shown that injection of NT into the PAG produced excitation of the NRM neurons. It is concluded that NT produces its analgesic effect by excitation of PAG neurons which leads to activation of the pain inhibitory system that originates from the NRM and its surrounding areas in the medulla.

Analgesics↗
PubMed1984

Autoradiographic distribution of nicotine receptors in rat brain.

The autoradiographic visualisation of 90%-specific tritiated nicotine binding to slide-mounted sections of rat brain is reported. Tritiated nicotine bound with high affinity (nanomolar Kd) and was selectively displaced by nicotinic agonists (e.g. L-nicotine approximately ACh greater than D-nicotine). The strikingly discrete distribution pattern obtained deviates from that of alpha-bungarotoxin, and suggests several possible roles for nicotinic transmission in the brain.

Alzheimer Disease↗
PubMed1984

In vivo autoradiography: visualization of stress-induced changes in opiate receptor occupancy in the rat brain.

A method of in vivo autoradiography was utilized which allows the visualization of local changes in opiate receptor occupation in the intact rat brain. The method is based on the exclusion of [3H]diprenorphine binding in areas in which the release of endogenous opiate peptides is increased by behavioral manipulation. The technique lends itself to the use of film autoradiography, allowing the mapping of relative levels of functional receptor occupancy throughout the whole brain. Prolonged intermittent footshock and forced swims in cold water (two stress-inducing manipulations which are known to release endogenous opiates) were found to cause highly significant decreases in specific high-affinity [3H]diprenorphine binding, as measured by liquid scintillation counting. These changes were unaccompanied by corresponding changes in non-specific binding and were not related to local changes in blood flow. A prolonged non-stressful swim in warm water caused no changes in [3H]diprenorphine binding. The use of tritium-sensitive film autoradiography allowed the resolution of these decreases to the level of individual nuclei. Differences in specific binding were found to be greatest in the periaqueductal gray, the reticular formation, and in midline-intralaminar thalamic nuclei, all of which have been implicated in the modulation of pain sensation.

Animals↗
PubMed1984

Neurochemical and behavioral effects of systemic and intranigral administration of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the rat.

At doses of 5-10 mg kg-1, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NMPTP) produces in rats acute immobility, retropulsion, straub tail, piloerection, exophthalmos, salivation and clonic movements of the forepaws. It does not produce analgesia as measured by the tail test, nor does it produce permanent motor impairment after chronic or intranigral administration. The acute retropulsion and immobilizing effects can be blocked by methysergide. Administered acutely, NMPTP doubles levels of serotonin in the raphe nucleus and substantia nigra. At the same time, levels of dopamine increase in the caudate nucleus and decrease in the substantia nigra. The NMPTP-induced decrease in dopamine content of the substantia nigra persists in chronically treated rats, but there is no significant decrease in striatal dopamine. After chronic administration of NMPTP, striatal levels of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were decreased by about 50%. Intranigral administrations of NMPTP (10 micrograms daily for 5 days) failed to produce a 6-hydroxydopamine-like lesion in the nigrostriatal system. These results indicate that NMPTP in the rat does not cause selective destruction of dopaminergic neurons, but it does produce acute tryptamine-like effects.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗