SEARCH · Search PubMed

Results for “Piriform Cortex”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 469 records · Page 26Linked to original sources

PubMed1990

Postnatal changes in the density and distribution of neurotensin-like immunoreactive fibers in the mediodorsal nucleus of the thalamus in the rat.

A previous report (Inagaki et al., Brain Res. 260:143-146, '83) suggested that the peptide neurotensin is contained in neurons of the piriform cortex that project to the mediodorsal thalamic nucleus (MD) in young rats. To confirm this, we have studied the distribution of neurotensin-like immunoreactive (NTIR) fibers in MD during development, using three antisera directed at different parts of the neurotensin molecule (Emson et al., J. Neurochem. 38:992-999, '82). In adult rats, NTIR fibers in MD are sparse. They are located mostly at the medial edge of MD and in the adjacent midline thalamic nuclei, with a few poorly stained NTIR fibers in the central part of MD. In contrast, during the first postnatal week, both the medial and central portions of MD stain heavily for neurotensin. The density of NTIR fibers in MD then progressively decreases until the density typical of adult rats is reached, at about 5 weeks. Changes in the distribution of NTIR fibers in MD also occur. In 7-day-old rats, the patches of NTIR fibers in the medial and central parts of MD are contiguous, but by 10 days a sparsely immunoreactive zone forms between them. With maturation, this zone enlarges as the density of neurotensin staining decreases, until the medial contingent of NTIR fibers reaches its adult position at the medial edge of MD. From a comparison of the distribution of NTIR cells with that of cells that can be retrogradely labeled from MD or the midline thalamus, the probable source of the NTIR fibers to the central part of MD is in the deep layer of the piriform cortex, while the NTIR fibers to the medial edge of MD and the midline nuclei may arise from the preoptic region and the medial amygdala. In neonatal rats, neurons are found in the piriform cortex, the preoptic region, and the medial amygdala, which can be double-labeled both for neurotensin and with a retrograde tracer injected into MD and the midline thalamus. Projections of the preoptic region to the thalamus have a distribution similar to that of the medial population of NTIR fibers, whereas the distribution of piriform cortical afferents in central MD matches the central patch of NTIR fibers.

Aging↗

PubMed2004

Olfactory system activation from sniffing: effects in piriform and orbitofrontal cortex.

Neuroimaging studies suggest that piriform cortex is activated at least in part by sniffing. We used H(2)(15)O positron emission tomography (PET) to study 15 healthy volunteers while they participated in four conditions, two of which were sniffing odorants and odorless air. The remaining two conditions involved a constant, very low flow of either odorized or odorless air during velopharyngeal closure (VPC), a technique that prevents subject-induced airflow through the nasal passages. Contrary to expectation, sniffing under odorless conditions did not induce significant piriform and surrounding cortical (PC+) activity when compared to odorless VPC, even at a liberal statistical threshold. However, a small correlation emerged in PC+ between the difference signal of [odorless sniffing - odorless VPC] and peak rate of nasal pressure change. PC+ activity was, however, strongly evoked by odorant exposure during sniffing and VPC, with neither technique showing greater activation. Activity in orbitofrontal (olfactory association) cortex was absent during odorant stimulation (OS) with VPC, but present during odorant sniffing. Sniffing may therefore play an important role in facilitating the higher-order analysis of odors. A right orbitofrontal region was also activated with odorless sniffing, which suggests a possible orbitofrontal role in guided olfactory exploration.

Adult↗

PubMed2001

Changes in the GABA-ergic system induced by trimethyltin application in the rat.

Ingestion of trimethyltin (TMT) produces mental confusion and temporal lobe seizures in humans. In rats, it causes increased seizure susceptibility, hyperactivity, aggression, learning impairment, and neuronal loss especially of hippocampal CA3c pyramidal cells and in the piriform cortex. As some of these symptoms may be due to impaired inhibitory neurotransmission, mRNA levels of the nine major GABA(A) receptor subunits, of GABA(B) receptors 1 and 2, and the 65- and 67-kD glutamate decarboxylase (GAD) variants were investigated by in situ hybridization 2, 5, and 16 days after TMT administration. GAD-65 mRNA levels were enhanced in hippocampal interneurons by up to 46% 5 days after TMT application, suggesting increased activity of respective neurons. In the granule cell layer, only the GABA(A) receptor subunit delta mRNA was altered (decreased by 48%). In the hippocampal sector CA3c and in the piriform cortex, mRNA levels of GABA(A) receptor subunits alpha1, alpha5, beta1, beta2, beta3, gamma2 and of both GABA(B) receptors declined (by 46-72%) after 5-16 days, being consistent with the extensive cell loss. In contrast, subunit alpha2 mRNA levels decreased already after 2 days at an extent exceeding the cell loss in CA3. Subunit alpha4 mRNA levels increased (about two-fold) in surviving CA3 neurons. In sector CA1, mRNA levels of subunits alpha1, alpha5, beta2, beta3, and gamma2 decreased by 35-54% in spite of only a minor (9%) cell loss. The data indicate neurodegeneration related decreases in mRNA levels in sector CA3 and piriform cortex, whereas decreases in sector CA1 may be a consequence of impaired excitatory input to this area.

Aggression↗

PubMed1993

Entorhinal cortex long-term potentiation evoked by theta-patterned stimulation of associative fibers in the isolated in vitro guinea pig brain.

Long-term potentiation (LTP) induced in the lateral entorhinal cortex by theta-patterned tetanic stimulation of the piriform cortex was analyzed in the isolated guinea pig brain maintained in vitro. Monosynaptic excitatory postsynaptic potentials (EPSPs) evoked by stimulation of the piriform cortex are composed of an early and late component selectively blocked by non-N-methyl-D-aspartate (non-NMDA) and NMDA receptor antagonists, respectively. LTP induction was dependent on NMDA receptor activation, being blocked by perfusing the preparation with 2-amino-5-phosphonovalerate (AP-5). LTP was expressed through synaptic enhancement of both early non-NMDA and late, possibly NMDA receptor-mediated responses.

2-Amino-5-phosphonovalerate↗

PubMed1988

Intrinsic connections of the retrohippocampal region in the rat brain: III. The lateral entorhinal area.

This paper describes the retrohippocampal projections of individual layers of the lateral entorhinal area as studied by the method of anterograde transport of the lectin Phaseolus vulgaris leucoagglutinin (PHA-L) in the rat. As in the medial entorhinal area (EA), (Köhler, '86a) PHA-L injections restricted to individual layers of the lateral EA resulted in labeling of sparse projections to the subicular complex (e.g., subiculum, pre- and parasubiculum), whereas projections to the perirhinal area and piriform cortex were prominent. All PHA-L injections resulted in the labeling of axons projecting longitudinally within the entorhinal area, in both dorsal and ventral directions, albeit the ventral projections were the most prominent ones. PHA-L injections into layers 2a and 2b resulted in labeling of axons that could be followed into layers 2a, 2b, and layer 1 on both sides of the injection site. Whereas numerous axons appeared to terminate in layer 2, most fibers ascended into layer 1, where they ran in a medial direction, passing the medial EA, around the parasubiculum to the presubiculum. Numerous axons were found to take a lateral route running past the lateral aspect of the lateral EA to the piriform cortex. The axons running medial in layer 2 did not enter the medial EA. After PHA-L injections into layer 3, a large number of axons left the labeled cells on both sides of the injection site, in addition to massive projections that ascended into layers 2b, 2a and 1, just above the injection. Few axons entered layers 2-6 of the medial EA, but numerous axons innervated layer 1, where they were found to run in the outer half of this layer. The axons running in a medial direction reached layer 1 of the presubiculum, whereas the laterally oriented ones innervated the molecular layer of the piriform cortex. PHA-L injections into layer 4 resulted in massive labeling of projections to all superficially located layers. Layers 1, and 2b through 5 were innervated lateral to, and layer 4 medial to, the injection site. After a PHA-L injection into layer 5, ascending projections were found innervating layers 1 through 4. The terminal fields were found to be particularly dense in the deep parts of layer 3 and in layer 1. This projection expanded laterally, but few projections reached into the medial sector of the lateral EA or into the medial EA.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1984

Evidence for the absence of impulse-regulating somatodendritic and synthesis-modulating nerve terminal autoreceptors on subpopulations of mesocortical dopamine neurons.

Electrophysiological and biochemical techniques were used to study midbrain dopamine systems. In the electrophysiological studies, projection areas of individual dopaminergic cells were identified by antidromic activation. Dopamine cells which innervate the piriform cortex and those that innervate the caudate nucleus demonstrated their usual dose-dependent inhibitory response to both the intravenous administration of the direct-acting dopamine agonist apomorphine and the microiontophoretic application of dopamine. In contrast, the firing rate of dopamine neurons which project to the prefrontal cortex and of those terminating in the cingulate cortex was not altered by either the intravenous administration of low to moderate doses of apomorphine or microiontophoretically applied dopamine. The mean basal discharge rate and degree of burst firing was also different between these subgroups of midbrain dopaminergic neurons. Mesoprefrontal and mesocingulate dopamine neurons had mean firing rates of 9.3 and 5.9 spikes/s respectively, and showed intense burst activity. Mesopiriform and nigrostriatal dopamine cells had discharge rates of 4.3 and 3.1 spikes/s and displayed only moderate bursting. The dopaminergic nature of those mesocortical neurons insensitive to apomorphine and dopamine was confirmed using combined intracellular recording and catecholamine histofluorescence techniques. Thus, after the intracellular injection of colchicine and subsequent processing for glyoxylic acid-induced histofluorescence, the injected cells could be identified by their brighter fluorescences compared to the surrounding, normally fluorescing, non-injected dopamine neurons. Using biochemical techniques, subgroups of midbrain dopaminergic systems were again found to differ. The administration of gamma-butyrolactone increased dopamine levels in all areas sampled (prefrontal, cingulate and piriform cortices as well as the caudate nucleus). However, although this effect was readily reversed in both the piriform cortex and caudate nucleus by pretreatment with apomorphine, this treatment had no effect on the increased dopamine levels observed in the prefrontal and cingulate cortices. In addition, the decline in dopamine levels after synthesis inhibition with alpha-methyltyrosine was significantly faster in the prefrontal and cingulate cortices relative to the caudate nucleus. The piriform cortex showed an intermediate decline which was not significantly different from that observed in any of the other regions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1990

VIP- and PHI-immunoreactivity in olfactory centers of the adult cat.

The purpose of the study was to determine the morphology and distribution of vasoactive intestinal polypeptide- and peptide histidine isoleucine-immunoreactive (VIP- and PHI-ir) neurons and innervation patterns in the main and accessory olfactory bulb, anterior olfactory nucleus, and piriform cortex of the adult cat. In these centers, VIP- and PHI-immunoreactive material are present in the same neuronal types, respectively, therefore summarized as VIP/PHI-ir neurons. In the main olfactory bulb, the majority of VIP/PHI-ir neurons are localized in the external plexiform layer. These neurons give rise to two or more locally branching axons. They form boutons on mitral and external tufted cell bodies. According to the morphology and location, we have classified these neurons as Van Gehuchten cells. Some VIP/PHI-ir neurons are present in the glomerular layer. They have small somata and give rise to dendrites branching exclusively into glomeruli. We have classified these neurons as periglomerular cells. In the granule cell layer, neurons with long apical dendrites and one locally projecting axon are present. In the accessory olfactory bulb, VIP/PHI-ir neurons are localized in the mixed external/mitral/internal plexiform layer. They represent Van Gehuchten cells. In the anterior olfactory nucleus and piriform cortex, VIP/PHI-ir bipolar basket neurons are present. They are localized mainly in layers II/III. These neurons are characterized by a bipolar dendritic pattern and by locally projecting axons forming basket terminals on large immunonegative cell somata. Because of their common morphological features, we summarize them as the retrobulbar VIP/PHI-ir interneuron population. The PHI-ir neurons display the same morphology as the VIP-ir cells. However, they are significantly lower in number with a ratio of VIP-ir to PHI-ir cells about 2:1 in the main and accessory olfactory bulb and in the anterior olfactory nucleus. By contrast, in the piriform cortex the ratio is about 1:1.

Animals↗

PubMed1993

Kindling in the perirhinal cortex.

In vitro experiments have indicated that the perirhinal cortex is highly excitable and its relationship to the basolateral amygdala and piriform cortex is altered by previous amygdala or dorsal hippocampal kindling. As a result, we felt it was important to assess the excitability of the perirhinal cortex in vivo by comparing its kindling profile to that of the basal amygdala, piriform cortex or dorsal hippocampus. We observed that the after-discharge (AD) threshold of the perirhinal cortex was higher than the other 3 structures but the AD duration was not different. Subsequently, the perirhinal cortex kindled more rapidly than the other 3 structures, and with extremely short latencies to onset of forelimb clonus. With the view that synchronized discharge in the perirhinal-piriform area provides the critical trigger for limbic kindled convulsions, the relationship of kindling rate and convulsion latencies and durations between the 4 structures was discussed.

Amygdala↗

PubMed1991

Parental behavior in the mouse: effects of lesions in the entorhinal/piriform cortex.

The effects of bilateral radiofrequency lesions in the region of the entorhinal and piriform cortex (ENT/PIR cortex) on pup-retrieving and ultrasound-elicited pup-searching behavior were investigated in ovariectomized estrogen-treated female mice, which were sensitized to pups by co-caring for a litter for 5 days together with the mother (FoEBex), as well as in primiparous lactating females (Flact). A further group of FoEBex were rendered anosmic by an intranasal treatment with zinc sulfate-solution before the sensitization period and tests for parental motivation. Both pup-retrieving and pup-searching behavior were disturbed to the same extent by ENT/PIR lesions and ZnSO4-induced anosmia in FoEBex. In Flact, however, pup-retrieving was not affected by the lesion, while ultrasound-recognition leading to pup-searching was disrupted. The present data suggest sensitization to pups as a case of olfactory learning and thus, the effects of the ENT/PIR lesions are regarded as anterograde olfactory amnesia. From the present data and results reported in the literature, it is suggested to differentiate between the neural substrates processing stimuli relevant for the appetitive component (pup-searching) of parental behavior (among others, the region of the entorhinal and piriform cortex), and the mechanisms regulating the consummatory component (pup-retrieving).

Animals↗

PubMed1998

Human brain function during odor encoding and recognition. A PET activation study.

In previous positron emission tomography (PET) studies we have shown significant regional cerebral blood flow (rCBF) increases during olfactory stimulation: unilaterally in the right orbitofrontal cortex, and bilaterally in the inferior frontal and temporal lobes (piriform cortex). In the present study we investigated brain function during different stages of olfactory memory processing. Subjects were scanned during four tasks: odor encoding, long-term odor recognition, short-term odor recognition and a no-odor sensorimotor control task. Subjects were 12 right-handed healthy volunteers (6 men, 6 women). Each subject underwent a training session four days prior to their PET scan to learn the six odors required for the long-term memory scan. PET scans were obtained with a Siemens Exact ECAT HR+ 3D system using H2(15)O methodology and 60-sec scanning intervals. PET images were coregistered with each subject's magnetic resonance imaging scan, averaged, and transformed into standard stereotaxic space. Paired image subtractions were analyzed for rCBF changes. Preliminary analyses have revealed significant activation of the right orbitofrontal region and bilateral piriform cortices during the long-term odor recognition task compared with the control task. Activation of the right piriform cortex was present during the short-term recognition task. Brain activity during encoding and retrieval tasks also involved prefrontal cortices. PET activation studies of memory in other modalities have led to hypotheses of a hemispheric encoding/retrieval asymmetry in frontal cortex; the generalizability of this theory to olfactory memory will be discussed.

Brain↗

PubMed2001

Epileptiform activity in the nucleus accumbens induced by GABA(A) receptor antagonists in rat forebrain slices is of cortical origin.

Extracellularly recorded field potentials, evoked by stimulation of cortico-nucleus accumbens border, were recorded in the nucleus accumbens (NAcc) in horizontal slices of rat ventral forebrain. The field excitatory postsynaptic potential (EPSP) event (N2) was calcium dependent, blocked by tetrodotoxin (1 microM), and reduced by over 70% by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10 microM), the antagonist of AMPA-type glutamate receptors. The EPSP amplitude was enhanced by either of the GABA(A) receptor antagonists, picrotoxin (10 microM; by 252+/-33%, n=18) and bicuculline methiodide (20 microM; by 216+/-34%, n=4). Additionally, picrotoxin (3-50 microM) and bicuculline methiodide (20 microM) promoted epileptiform activity within the NAcc, manifest as the emergence of additional late components, N3, N4 and N5, in the evoked synaptic waveform. In slices with the frontal cortex removed, picrotoxin (10-50 microM) and bicuculline methiodide (20 microM) were unable to promote epileptiform activity within the NAcc, although a smaller increase in the peak amplitude of the field EPSP (163+/-18%, n=6) was observed at the highest concentrations of picrotoxin (50 microM). Histological examination of the slice demonstrated that in such decorticated slices, the piriform cortex (PC) had been removed. We propose that stimulation of the cortico-NAcc border not only evokes an orthodromic EPSP in the NAcc, but also causes antidromic activation of cortical tissue. Disinhibition by GABA(A) antagonists of circuits intrinsic to the cortex, possibly the piriform cortex, is the principal cause of the facilitation of the EPSP and of regenerative epileptiform activity in NAcc evoked by stimulation of cortical input.

Animals↗

PubMed1997

Deafferentation causes apoptosis in cortical sensory neurons in the adult rat.

The present study provides an experimental model of the apoptotic death of pyramidal neurons in rat olfactory cortex after total bulbectomy. Terminal transferase (TdT)-mediated deoxyuridine triphosphate (d-UTP)-biotin nick end labeling (TUNEL), DNA electrophoresis, and neuronal ultrastructure were used to provide evidence of apoptosis; neurons in olfactory cortex were counted by stereology. Maximal TUNEL staining occurred in the piriform cortex between 18 and 26 hr postbulbectomy. Within the survival times used in the present study (up to 48 hr postlesion), cell death was observed exclusively in the piriform cortex; there was no evidence of cell death in any other areas connected with the olfactory bulb. Neurons undergoing apoptosis were pyramidal cells receiving inputs from, but not projecting to, the olfactory bulb. The apical dendrites of these neurons were contacted by large numbers of degenerating axonal terminals. Gel electrophoresis of DNA purified from lesioned olfactory cortex showed a ladder pattern of fragmentation. Inflammatory cells or phagocytes were absent in the environment of degenerating neurons in the early stages of the apoptotic process. The present model suggests that deafferentation injury in sensory systems can cause apoptosis. In addition, olfactory bulbectomy can be used for investigating molecular mechanisms that underlie apoptosis in mature mammalian cortical neurons and for evaluating strategies to prevent the degeneration of cortical neurons.

Afferent Pathways↗

PubMed2004

Olfactory fear conditioning induces field potential potentiation in rat olfactory cortex and amygdala.

The widely used Pavlovian fear-conditioning paradigms used for studying the neurobiology of learning and memory have mainly used auditory cues as conditioned stimuli (CS). The present work assessed the neural network involved in olfactory fear conditioning, using olfactory bulb stimulation-induced field potential signal (EFP) as a marker of plasticity in the olfactory pathway. Training consisted of a single training session including six pairings of an odor CS with a mild foot-shock unconditioned stimulus (US). Twenty-four hours later, the animals were tested for retention of the CS as assessed by the amount of freezing exhibited in the presence of the learned odor. Behavioral data showed that trained animals exhibited a significantly higher level of freezing in response to the CS than control animals. In the same animals, EFPs were recorded in parallel in the anterior piriform cortex (aPC), posterior piriform cortex (pPC), cortical nucleus of the amygdala (CoA), and basolateral nucleus of the amygdala (BLA) following electrical stimulation of the olfactory bulb. Specifically, EFPs recorded before (baseline) and after (during the retention test) training revealed that trained animals exhibited a lasting increase (present before and during presentation of the CS) in EFP amplitude in CoA, which is the first amygdaloid target of olfactory information. In addition, a transient increase was observed in pPC and BLA during presentation of the CS. These data indicate that the olfactory and auditory fear-conditioning neural networks have both similarities and differences, and suggest that the fear-related behaviors in each sensory system may have at least some distinct characteristics.

Amygdala↗

PubMed2000

Olfactory inputs activate the medial entorhinal cortex via the hippocampus.

The lateral and medial regions of the entorhinal cortex differ substantially in terms of connectivity and pattern of activation. With regard to olfactory input, a detailed and extensive physiological map of the olfactory projection to the entorhinal cortex is missing, even if anatomic studies suggest that the olfactory afferents are confined to the lateral and rostral entorhinal region. We studied the contribution of the medial and lateral entorhinal areas to olfactory processing by analyzing the responses induced by lateral olfactory tract stimulation in different entorhinal subfields of the in vitro isolated guinea pig brain. The pattern of synaptic activation of the medial and lateral entorhinal regions was reconstructed either by performing simultaneous multisite recordings or by applying current source density analysis on field potential laminar profiles obtained with 16-channel silicon probes. Current source density analysis demonstrated the existence of a direct monosynaptic olfactory input into the superficial 300 microm of the most rostral part of the lateral entorhinal cortex exclusively, whereas disynaptic sinks mediated by associative fibers arising from the piriform cortex were observed at 100-350 microm depth in the entire lateral aspect of the cortex. No local field responses were recorded in the medial entorhinal region unless a large population spike was generated in the hippocampus (dentate gyrus and CA1 region) by a stimulus 3-5x the intensity necessary to obtain a maximal monosynaptic response in the piriform cortex. In these conditions, a late sink was recorded at a depth of 600-1000 microm in the medial entorhinal area (layers III-V) 10.6 +/- 0.9 (SD) msec after a population spike was simultaneously recorded in CA1. Diffuse activation of the medial entorhinal region was also obtained by repetitive low-intensity stimulation of the lateral olfactory tract at 2-8 Hz. Higher or lower stimulation frequencies did not induce hippocampal-medial entorhinal cortex activation. These results suggest that the medial and the lateral entorhinal regions have substantially different roles in processing olfactory sensory inputs.

Action Potentials↗

PubMed1999

Arterial supply of limbic structures in the guinea pig.

This study outlines the vascular territories of the cerebral arteries that originate from the Willis circle to supply limbic structures in the guinea pig brain. The entire cerebral vascular system was visualized in four preliminary experiments by performing superselective microangiographic studies with iodine contrast medium perfusion of the whole brain after in vitro isolation according to a technique described previously (de Curtis et al. [1991] Hippocampus 1:341-354). Subsequently, the perfusion territory of the different arteries that originate from the Willis circle was characterized after cannulation and perfusion of individual arteries with a gelatin solution that contained waterproof black ink. The analysis was performed by identifying the brain regions that contained the black stain on 150-microm-thick coronal sections that were cut after brain fixation with paraformaldehyde for at least 1 week. The middle cerebral artery and the rostral and caudal posterior cerebral arteries supply the limbic cortices and some related subcortical regions. In particular, large portions of the hippocampal formation are supplied by both the rostral posterior cerebral artery and the rostral branch of the caudal posterior cerebral artery, whereas the ventral temporal part of the hippocampus is served exclusively by the rostral posterior cerebral artery. The amygdala, the periamygdaloid cortex, and the piriform cortex are served by the middle cerebral artery and in part by the perforating arteries. The entorhinal, perirhinal, and postrhinal cortices are vascularized by the posterior and middle cerebral arteries, with a very broad overlap between the distal territories of these vessels. The demonstration of an extensive superimposition between the arterial supply of the entorhinal and the perirhinal regions suggests the presence of anastomotic connections that potentially are protective against ischemic events. Such an arrangement was not observed for the arteries that supply the ventral portion of the hippocampal formation and the basolateral amygdala, which showed nonoverlapping boundaries. The pathophysiological consequences of a similar vascular organization are discussed.

Animals↗

PubMed1990

Regulation of dopamine and serotonin synthesis by acute administration of cocaine.

Because cocaine effectively increases extracellular levels of both dopamine (DA) and serotonin (5HT), it might be expected that this agent would inhibit transmitter biosynthesis in these monoamine neurons by activation of autoregulatory feedback pathways. This possibility was tested by measuring the effect of cocaine on 3,4-dihydroxyphenylalanine accumulation (DA synthesis) and 5-hydroxytryptophan accumulation (5HT synthesis) in vivo and in vitro after inhibition of aromatic amino acid decarboxylase with NSD-1015. In vivo, cocaine suppressed both DA and 5HT synthesis in a dose-dependent (10-60 mumols/kg, i.p.) and time-dependent fashion (maximum 60 min after administration, recovery by 120-150 min). Inhibition of DA and 5HT synthesis ranged from 35% to 60% depending on the brain region and was apparent in dopaminergic fields such as the medial prefrontal cortex, nucleus accumbens, piriform cortex, striatum, and in noradrenergic fields, such as the hippocampus and temporal cortex. Inhibition of DA, but not 5HT, synthesis was blocked by the D2 antagonist sulpiride in brain areas containing DA nerve terminals. Procaine (30 mumols/kg) did not inhibit DA or 5HT synthesis and prior treatment with reserpine diminished the effectiveness of cocaine in the medial prefrontal cortex, but not in the striatum. Cocaine did not reverse the gamma-butyrolactone-induced increase in striatal DA synthesis nor did cocaine block the ability of the D2 agonist quinpirole to reverse the increase. In vitro, cocaine inhibited DA synthesis in depolarized (K+ = 30 mM) striatal brain slices, an effect that was reversed by the D2 antagonist eticlopride. These results suggest that DA and 5HT neurons compensate in situ for cocaine-induced increases in synaptic transmitter levels by a transient inhibition of transmitter biosynthesis. Acute suppression of transmitter synthesis (and release) in mesoprefrontal DA neurons may represent the principal compensatory mechanism in this group of neurons.

Animals↗

PubMed1987

D-2 dopamine-receptors regulate the release of [3H]dopamine in rat cortical regions showing dopamine immunoreactive fibers.

Using an antibody raised against dopamine the occurrence of dopamine-containing fibers was demonstrated in the prefrontal cortex, anterior cingulate cortex, parietal neocortex, piriform cortex and entorhinal cortex. In extracts of these cortical regions significant amounts of dopamine, although approximately a 100-fold less than in the neostriatum or nucleus accumbens, were detected with high performance liquid chromatography. The release of [3H]dopamine from slices of all these cortical regions was studied in vitro in a superfusion system and desipramine was used to prevent the uptake of [3H]dopamine in noradrenergic nerve terminals. It appeared that the electrically evoked release of radioactivity was inhibited by drugs stimulating D-2 dopamine-receptors in all the regions studied. Cation-exchange column chromatography revealed that the radioactivity released consisted predominantly of [3H]dopamine, indicating that D-2 receptors mediate the inhibition of the release of [3H]dopamine from dopaminergic nerve terminals. Likewise, in the neostriatum as well as in the nucleus accumbens D-2 receptor stimulation inhibits the release of [3H]dopamine. Therefore it is our conclusion that D-2 receptors regulate the release of dopamine from dopaminergic neurons originating in the ventral tegmental area as well as in the substantia nigra.

Animals↗

PubMed1994

Protective effect of bifemelane on c-Fos-like immunoreactivity in rat cerebral ischemia.

Cytoprotection by bifemelane hydrochloride was investigated immunohistochemically in the cerebral cortex of rats during ischemia. The middle cerebral artery was occluded for 30 min and then reperfused for 6 h. c-Fos-like immunoreactive neurons were found in layers II to VI of the cerebral cortex and were especially abundant in the parietal cortex and the piriform cortex on the side of the occlusion. In sham-operated control rats, a few c-Fos-like immunoreactive neurons were seen in the ipsilateral side of the cerebral cortex. In animals that had been injected with bifemelane hydrochloride (20 mg/kg, IP) 30 min before the onset of ischemia and 90 min after reperfusion, the number of c-Fos-like immunoreactive neurons was significantly reduced in the cerebral cortex. The results suggest that bifemelane hydrochloride can inhibit the ischemia-induced increase in c-Fos-like immunoreactivity in cerebral cortex neurons.

Animals↗