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H C Fibiger

Publications and source records attributed to H C Fibiger.

At least 127 records · Page 7Linked to original sources
PubMed1988

Ontogeny of histidine-decarboxylase-immunoreactive neurons in the tuberomammillary nucleus of the rat hypothalamus: time of origin and development of transmitter phenotype.

The ontogeny of the histidine decarboxylase (HDC)-immunoreactive neurons of the tuberomammillary (TM) nucleus was studied in the rat brain. The time of origin of TM neurons was studied by counting the percentage of HDC-immunopositive neurons double labelled by autoradiography in adult progeny of dams injected with [3H]-thymidine at various times during gestation. Neurogenesis began on embryonic day (E) 13, peaked on E16, and was complete by E18. HDC immunoreactivity was first detected in the fetal rat brain on E16. Experiments utilizing short-survival [3H]-thymidine autoradiography combined with HDC immunohistochemistry demonstrated that TM neurons undergo their final mitotic division prior to expression of their transmitter phenotype.

Animals↗
PubMed1988

Comparison between short- and long-term haloperidol administration on somatostatin and substance P concentrations in the rat brain.

Neuroleptics influence a variety of putative neurotransmitters in the basal ganglia, including somatostatin and substance P. Most studies have been performed in animals after only 3 or 4 weeks of neuroleptic administration and have seldom examined the effects of withdrawal. To understand better the effects of haloperidol on neuropeptide systems, the effects of short-term (3 weeks) and long-term (8 months) administration, as well as withdrawal from long-term administration of haloperidol, on somatostatin and substance P concentrations were examined in the rat. Short-term haloperidol significantly decreased the concentrations of somatostatin in the caudate-putamen, nucleus accumbens, and ventral tegmental area, and decreased the concentration of substance P in the substantia nigra and the nucleus accumbens. However, long-term administration only decreased the concentration of somatostatin in the nucleus accumbens. In addition, a slight reduction in the concentration of substance P in the medial prefrontal cortex was detected after long-term treatment. After withdrawal from long-term haloperidol administration the concentrations of these peptides did not differ from control values in any of the brain regions examined. These results confirm that dopamine receptor blockade can affect the somatostatin and substance P systems in the basal ganglia and indicate that during long-term administration (8 months) tolerance develops to some of the effects that are observed after shorter (3 weeks) treatment periods.

Animals↗
PubMed1988

Time of origin of cholinergic neurons in the rat basal forebrain.

The timing of the final mitotic division of basal forebrain cholinergic neurons was studied by injecting [3H]thymidine into timed pregnant rats and processing the brains of their progeny as young adults for immunohistochemistry with a monoclonal antibody to choline acetyltransferase (ChAT) followed by autoradiography. ChAT-positive neurons located caudally in the basal forebrain were found to become postmitotic mostly on embryonic (E) days 12 and 13, whereas the peak final mitosis of more rostrally located ChAT-positive neurons occurred increasingly later, with the most rostral ChAT-immunoreactive neurons leaving their final mitotic cycles on E15 and E16. In all basal forebrain regions, cholinergic neurogenesis was complete by E17. These results indicate that the cholinergic neurons in the basal forebrain become postmitotic in a caudal-to-rostral gradient over about 5 days. The continuity of the gradient suggests that these cholinergic neurons may derive from the same germinal source.

Animals↗
PubMed1988

Brainstem afferents to the magnocellular basal forebrain studied by axonal transport, immunohistochemistry, and electrophysiology in the rat.

Brainstem afferents to the magnocellular basal forebrain were studied by using tract tracing, immunohistochemistry and extracellular recordings in the rat. WGA-HRP injections into the horizontal limb of the diagonal band (HDB) and the magnocellular preoptic area (MgPA) retrogradely labelled many neurons in the pedunculopontine and laterodorsal tegmental nuclei, dorsal raphe nucleus, and ventral tegmental area. Areas with moderate numbers of retrogradely labelled neurons included the median raphe nucleus, and area lateral to the medial longitudinal fasciculus in the pons, the locus ceruleus, and the medial parabrachial nucleus. A few labelled neurons were seen in the substantia nigra pars compacta, mesencephalic and pontine reticular formation, a midline area in the pontine central gray, lateral parabrachial nucleus, raphe magnus, prepositus hypoglossal nucleus, nucleus of the solitary tract, and ventrolateral medulla. A similar but not identical distribution of labelled neurons was seen following WGA-HRP injections into the nucleus basalis magnocellularis. The possible neurotransmitter content of some of these afferents to the HDB/MgPA was examined by combining retrograde Fluoro-Gold labelling and immunofluorescence. In the mesopontine tegmentum, many retrogradely labelled neurons were immunoreactive for choline acetyltransferase. In the dorsal raphe nucleus, some retrogradely labelled neurons were positive for serotonin and some for tyrosine hydroxylase (TH); however, the majority of retrogradely labelled neurons in this region were not immunoreactive for either marker. The ventral tegmental area, substantia nigra pars compacta, and locus ceruleus contained retrogradely labelled neurons which were also immunoreactive for TH. Of the retrogradely labelled neurons occasionally observed in the nucleus of the solitary tract, prepositus hypoglossal nucleus, and ventrolateral medulla, some were immunoreactive for either TH or phenylethanolamine-N-methyltransferase. To characterize functionally some of these brainstem afferents, extracellular recordings were made from antidromically identified cortically projecting neurons, mostly located in the HDB and MgPA. In agreement with most previous studies, about half (48%) of these neurons were spontaneously active. Electrical stimulation in the vicinity of the pedunculopontine tegmental and dorsal raphe nuclei elicited either excitatory or inhibitory responses in 21% (13/62) of the cortically projecting neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1988

Non-cholinergic basal forebrain neurons project to the contralateral basal forebrain in the rat.

Following injections of wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) or the fluorescent tracer fluoro-gold into the magnocellular preoptic area and the horizontal limb of the diagonal band, retrogradely labelled neurons were found in the homotopic region of the contralateral basal forebrain. Labelled fibers apparently arising from these neurons travelled in the stria medullaris and the habenular commissure to terminate in the contralateral basal forebrain. Although the neurons retrogradely labelled with fluoro-gold in the contralateral basal forebrain were similar in size to choline acetyltransferase (ChAT)-immunoreactive neurons, and were intermingled with them, none was ChAT-positive. WGA-HRP injections into the nucleus basalis magnocellularis did not result in retrograde labelling in the contralateral basal forebrain. These findings suggest that non-cholinergic neurons may serve as a direct link between the two sides of selective magnocellular basal forebrain regions.

Animals↗
PubMed1988

Chronic haloperidol administration increases the density of D2 dopamine receptors in the medial prefrontal cortex of the rat.

Rats received haloperidol (1.3-1.5 mg/kg/day) via their drinking water for 21 weeks. At the end of this period the density of D2 dopamine receptors and their affinity for [3H]-spiperone were measured in the striatum and medial prefrontal cortex. The chronic haloperidol treatment increased the density of D2 receptors in the striatum by 70% and in the medial prefrontal cortex by 50%. The chronic haloperidol did not significantly alter the apparent affinity of D2 receptors for [3H]-spiperone in either structure. These results indicate that the density of D2 receptors in the medial prefrontal cortex is influenced by chronic exposure to haloperidol in a manner that is very similar to the well-documented increase that occurs in the striatum.

Animals↗
PubMed1988

Independence of amphetamine reward from locomotor stimulation demonstrated by conditioned place preference.

The conditioned place preference (CPP) paradigm is used widely as a measure of a drug's rewarding properties. The present study examined whether the CPP produced by amphetamine is dependent on the locomotor stimulation that is produced by the drug. An earlier study (Swerdlow and Koob 1984) found that interfering with locomotor stimulation using restraint during the drug treatment blocked CPP. The present study examined whether this effect of restraint was indeed due to restriction of locomotion or was due to restraint maintaining the stimulus novelty of the CPP apparatus. The first experiment showed that novelty of the apparatus itself was a potent factor in the CPP paradigm and was capable of producing a place preference. The second experiment showed that restraint alone could produce a CPP, as would be expected if it maintained stimulus novelty of the apparatus. It also showed that although a CPP to amphetamine could be blocked by restraining the animals during drug treatment, prior habituation to the apparatus to reduce stimulus novelty before treatment negated the effect of restraint on amphetamine CPP. These results indicate that rats can demonstrate a CPP produced by amphetamine even when their activity is restrained. This suggests that the drug's rewarding properties are not dependent on locomotor stimulation.

Amphetamine↗
PubMed1988

A role for the mesolimbic dopamine system in the reinforcing properties of diazepam.

The conditioned place preference paradigm was used to investigate the neurochemical and neuroanatomical substrates which mediate the rewarding properties of diazepam. The results confirmed that diazepam (1 and 2.5 mg/kg, IP) produced place preference for a distinctive environment that had previously been paired with injections of the drug. Pretreatment with haloperidol (0.1 mg/kg) antagonised the place preference induced by diazepam (1 mg/kg). Pretreatment with domperidone (2 mg/kg) failed to influence this effect of diazepam. Haloperidol (0.1 mg/kg) and domperidone (2 mg/kg) alone did not produce place aversion. In separate experiments the diazepam-induced place preference was examined in rats having 6-hydroxydopamine (6-OHDA) lesions of the nucleus accumbens. These animals did not show preference for the compartment associated with diazepam. Depletion of central noradrenaline produced by systemic injections of DSP4 did not affect diazepam-induced place preference conditioning. These findings suggest that dopamine-containing neurons of the mesolimbic system are a component of the neural circuitry that mediates the reinforcing properties of diazepam.

Animals↗
PubMed1988

Anatomical analysis of the involvement of mesolimbocortical dopamine in the locomotor stimulant actions of d-amphetamine and apomorphine.

Lesion studies employing 6-hydroxydopamine (6-OHDA) suggest that locomotor hyperactivity induced by certain stimulant drugs is dependent on dopaminergic neurotransmission in the nucleus accumbens (NACC). However, studies to date have not adequately controlled for the reported effects of 6-OHDA on baseline (non-drug) activity and on DA levels in other terminal regions. Slow bilateral infusions of 6-OHDA into the NACC, but not into olfactory tubercle (OT) or medial prefrontal cortex (mPFCx), reduced d-amphetamine (0.5 mg/kg SC) hyperactivity and resulted in a "supersensitive" (hyperactive) response to a low dose of apomorphine (0.1 mg/kg SC) in photocell cages. Direct observation revealed no behavioral changes in OT lesioned rats challenged with apomorphine which might correspond to a "denervation supersensitivity" syndrome. Assays of DA and 5-hydroxytryptamine (5-HT) in mPFCx, OT, NACC, and caudate-putamen revealed that 6-OHDA infusion into NACC caused substantial DA loss in NACC, OT and mPFCx, whereas infusion at mPFCx or OT sites depleted DA locally (greater than 85% loss) with little or no remote change. Concentrations of 5-HT were little altered by 6-OHDA, except for a local depletion in mPFCx. The present results confirm the importance of nucleus accumbens DA in the expression of locomotor stimulation induced by apomorphine and d-amphetamine, and suggest that the mPFCx and OT do not make an important contribution.

Animals↗
PubMed1988

Fentanyl-induced conditional place preference: lack of associated conditional neurochemical events.

Three experiments were performed to determine if stimuli previously paired with the reinforcing effects of fentanyl elicit changes in the activity of dopaminergic neurons that are similar to the unconditional effects of the drug. Experiment 1 characterized the unconditional effects of fentanyl (0.04 mg/kg SC) on neurochemical indices of dopaminergic activity in rats. Both acute and repeated fentanyl injections (five injections administered at 48-h intervals) increased the concentrations of the dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) within the striatum (STR), nucleus accumbens (NAS), and olfactory tubercle (OT). Acute injections elicited a greater increase in metabolite concentrations in the NAS than in the STR, suggesting that there are regional differences in the sensitivity of dopaminergic neurons to fentanyl. In experiments 2 and 3, fentanyl (five injections; 0.04 mg/kg SC) was paired with environmental stimuli using a place preference conditioning paradigm. The fentanyl-paired stimuli failed to elicit conditional changes in DOPAC or HVA concentrations within the STR, NAS, or OT even though rats exhibited a preference for the drug-paired compartment of the shuttle box. These results indicate that the secondary reinforcing effects of stimuli previously paired with fentanyl may not reflect the ability of these stimuli to elicit measurable changes in the activity of mesolimbic or nigrostriatal dopaminergic neurons.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

On the role of the dorsal noradrenergic bundle in learning and habituation to novelty.

In Experiment 1, the performance of vehicle control rats and rats with 6-hydroxydopamine-induced lesions of the dorsal noradrenergic bundle (DB) was examined in acquisition and extinction of bar pressing and in spontaneous and food-reinforced alternation in a T-shape maze. Plasma corticosterone levels in basal conditions, after chronic food restriction, after transportation to a novel environment, and after sessions of either rewarded or nonrewarded bar pressing were assayed. DB lesions produced a significant decrease of spontaneous alternation and a significant but small resistance to extinction, without reliably altering either corticosterone responses or instrumental spatial alternation. In Experiment 2, bar-press extinction and instrumental alternation were reexamined in new groups of control rats and rats with DB lesions without any blood collection procedures. The DB lesions did not reliably alter either behaviors on any measures. Taken together, these data indicate no consistent effects of forebrain noradrenaline depletion on either extinction or spatial memory or pituitary-adrenocortical function. However, the impairment of spontaneous alternation found in a previous study was confirmed. These findings are discussed in terms of the proposed roles of the dorsal noradrenergic bundle in learning and habituation to novelty.

Animals↗
PubMed1988

Conditioned circling in rats: bilateral involvement of the mesotelencephalic dopamine system demonstrated following unilateral 6-hydroxydopamine lesions.

High rates of conditioned circling have previously been associated with a bilateral augmentation of striatal dopamine metabolism. These results suggest that both striata subserve this response. The present experiment further assessed this possibility by determining the effects of unilateral 6-hydroxydopamine lesions of the mesotelencephalic dopamine system on conditioned circling. Rats were initially trained to circle in their preferred direction for water reinforcement. Upon establishment of this response, they received unilateral lesions at the level of the lateral hypothalamus either contralateral or ipsilateral to the reinforced direction of circling. Reinforced responding was virtually abolished in rats with contralateral lesions. In contrast, rats lesioned ipsilateral to the direction of reinforced circling exhibited only a 50% decrease in rate of reinforced responding. Non-reinforced responding was increased only in rats with contralaterally placed lesions. Following 5 postoperative test sessions, the experimental contingencies were reversed. 'Ipsilaterally lesioned' rats were now required to circle away from their lesion whereas 'contralaterally lesioned' rats had to turn towards their lesion. The 'Contralateral' group acquired the reversal, such that reinforced responding occurred more frequently than non-reinforced responding. However, reinforced rates of responding did not reach preoperative rates. Conversely, 'ipsilaterally lesioned' rats could not learn to turn contraversively and now made more non-reinforced than reinforced responses. These findings suggest that conditioned circling is mediated by a bilateral involvement of the mesotelencephalic dopaminergic systems. However, the specific role of each side appears to be dependent upon its relationship with the direction of circling emitted.

Animals↗
PubMed1988

Different times of origin of choline acetyltransferase- and somatostatin-immunoreactive neurons in the rat striatum.

Two populations of aspiny interneurons have been identified in the mammalian striatum, one cholinergic and the other using the neuropeptide somatostatin as a neurotransmitter. The times at which these 2 cell populations undergo their final mitosis were studied by injecting tritiated thymidine into timed pregnant rats and then processing the brains of the progeny as young adults for immunohistochemistry with monoclonal antibodies to choline acetyltransferase and somatostatin followed by autoradiography. Choline acetyltransferase-immunoreactive neurons became postmitotic in a caudal-to-rostral gradient; the occurrence of final mitosis was maximal on embryonic day (E) 12 at the most caudal level and on E15 at the most rostral. A more subtle lateral-to-medial gradient was also observed in the precommissural striatum. In contrast, no obvious gradients were seen with somatostatin-immunoreactive neurons; regardless of their location within the striatum, these neurons underwent their final mitosis on days E15-16, towards the end of cholinergic neurogenesis. These results indicate that although both cholinergic and somatostatin-containing cells represent interneuronal populations in the striatum, they display distinctly different spatiotemporal patterns of neurogenesis.

Animals↗
PubMed1988

Evidence that mesolimbic dopaminergic activation underlies the locomotor stimulant action of nicotine in rats.

L-Nicotine stimulates locomotor activity in rats which have had prior experience of the drug. The present study investigated whether this behavioral effect is related to activation of the mesolimbic dopamine system. In the first experiment, l-nicotine (0.2-0.8 mg/kg s.c.) stimulated locomotor activity and increased dopamine utilization in the olfactory tubercle, as judged by the ratio of the concentration of dihydroxyphenylacetic acid to dopamine. In other experiments, l-nicotine (0.1-0.4 mg/kg) stimulated locomotor activity in a dose-related, stereoselective manner; after pretreatment with the l-aromatic amino acid decarboxylase inhibitor NSD-1015, l-nicotine increased 3,4-dihydroxyphenylalanine/dopamine ratios in olfactory tubercle and nucleus accumbens, suggesting increased dopamine utilization, although absolute concentrations of 3,4-dihydroxyphenylalanine and dopamine were in general not significantly altered. This neurochemical action of l-nicotine was dose-dependent, stereoselective and absent in the caudate-putamen at the doses tested. l-Nicotine did not alter indices of 5-hydroxytryptamine utilization. The locomotor stimulant effect of l-nicotine was abolished by bilateral intra-accumbens microinjection of 6-hydroxydopamine, which depleted markedly mesolimbic terminal areas of dopamine. Thus, in rats which have been chronically treated with l-nicotine, a selective activation of mesolimbic dopamine appears to mediate the locomotor stimulant effect of this drug.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Distribution and organization of cholinergic neurons in the rat forebrain demonstrated by computer-aided data acquisition and three-dimensional reconstruction.

An understanding of the organization of cholinergic neurons in the central nervous system has been an important objective for many years. By developing and applying a new electronic method for mapping tissue sections, we have generated original graphic and quantitative findings on forebrain cholinergic neurons that provide new insight into their distribution and organization. Satoh, Armstrong, and Fibiger (Brain Res. Bull. 11:693-720, 1983) have proposed that in the basal forebrain cholinergic neurons with long axons form a continuum rather than being arranged as a series of discrete nuclear groups. It has been difficult, however, by conventional methods of data analysis and display, to test this hypothesis. By using a digital microscopy system, the position of every cholinergic neuron was marked with 1-micron resolution in tissue sections taken at 90-microns or 180-microns intervals through the entire distribution of these neurons in the forebrain. The three-dimensional reconstruction of these neurons in context shows them to be distributed as a continuous cell column. The column twists and changes position as it is deformed by adjacent neuronal structures, such that its shape and continuity would not be apparent without reconstruction into a computer graphics model. Complementary analyses of the distribution of cholinergic interneurons in dopamine-rich regions of the forebrain indicated that there are regional differences between striatal and olfactory tubercle neurons. Cellular morphometry analyses show the population of cholinergic neurons in the rat to be surprisingly homogenous in size, but not in shape. Graphic and quantitative analyses indicated that there is a striking relationship between the distributions of projection and interneuronal cell groups. We conclude that the basal forebrain cholinergic neurons form a continuum. The chemoarchitecture of this cell group does not conform to the usual cytoarchitectural divisions. The present results, however, taken together with the findings based on Nissl-stained sections and connectional and biochemical data, suggest that the region of this neurochemically defined continuum should be reexamined for consideration as a single functional entity or nucleus: a cholinergic basal nuclear complex.

Animals↗
PubMed1987

Tolerance to haloperidol-induced increases in dopamine metabolites: fact or artifact?

Haloperidol increased 3,4-dihydroxyphenylacetic acid and homovanillic acid concentrations in the striatum, nucleus accumbens and olfactory tubercle of both drug-naive rats and rats pretreated with haloperidol (10 injections). The increases in metabolite concentrations were greater in all brain regions of the naive rats, suggesting that haloperidol pretreatment resulted in a decreased responsiveness to the drug (tolerance). However, subchronic haloperidol injections also resulted in decreased basal metabolite concentrations in rats killed 48 h after the last injection. While the response of drug-experienced rats to haloperidol was attenuated relative to that of drug-naive rats, this difference could be accounted for entirely by the decreased basal metabolite concentrations that occur after repeated haloperidol injections.

3,4-Dihydroxyphenylacetic Acid↗