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H C Fibiger

Publications and source records attributed to H C Fibiger.

At least 37 records · Page 2Linked to original sources
PubMed1995

Cocaine and d-amphetamine increase c-fos expression in the rat cerebellum.

Psychostimulant drugs have been reported to increase the expression of some immediate-early genes in the cerebellum. In the present study, immunohistochemical techniques were used to assess the pattern of c-fos expression in the cerebellum produced by d-amphetamine or cocaine. Systemic administration of d-amphetamine (1.5, 6 mg/kg) or cocaine (10, 20 mg/kg) increased locomotor activity, which at low doses was blocked by pretreatment with the dopamine D1 receptor antagonist SCH 23390 (1 mg/kg). Within the cerebellum, basal levels of c-fos expression were abolished by SCH 23390, with the exception of lobule VI. Dose-dependent increases in Fos-like immunoreactivity were elicited by d-amphetamine and cocaine. Pretreatment with SCH 23390 greatly reduced the extent to which either stimulant increased c-fos expression. Psychostimulant-induced Fos-like immunoreactive nuclei were generally restricted to the granule cell layer within each of the midvermal cerebellar lobules (I-X), although occasional nuclei were found in the Purkinje cell layer. In addition, a homogeneous pattern of Fos-like immunoreactive nuclei, of sparse density, was also found near the pial surface of the molecular layer following d-amphetamine but not cocaine. Within the granule cell layer dense clusters of Fos-like immunoreactive neurons extended from the molecular layer to the Purkinje cell layer and were found at both the pial surface as well as in the deep portions of individual folia. These data add to a growing body of evidence indicating that the induction of regionally specific alterations in c-fos expression by psychostimulants is mediated via a D1 receptor mechanism.

Animals↗
PubMed1995

Neurochemical heterogeneity of the primate nucleus accumbens.

In order to further investigate the neurochemical anatomy of the primate nucleus accumbens (NAC), the distributions of the neuropeptides leucine-enkephalin (Leu-ENK), neurotensin (NT), and substance P (SP) and of haloperidol-induced c-fos expression were investigated in the macaque monkey using immunohistochemical methods. To define the boundaries of the NAC, dopamine (DA) and tyrosine hydroxylase (TH) immunohistochemistry was performed. In addition, to formulate the distinction between subdivisions of the nucleus accumbens, immunohistochemistry for calbindin-D28 (CBD) and SP was employed. In general, the medial part of NAC, which consisted of small to medium-sized cells, was low for CBD immunoreactivity and moderate to high for SP immunoreactivities, while the dorsolateral part, which was composed of small cells, showed the opposite pattern of immunostaining for CBD and SP. Many Leu-ENK-immunoreactive perikarya were observed in the dorsal NAC at its middle and caudal levels. There were moderate densities of Leu-ENK-positive fibers throughout the medial part of the NAC. At the dorsolateral margin of the NAC, Leu-ENK-positive fibers formed patches. Most NT-positive perikarya were found in the dorsolateral subdivision. SP-positive perikarya were scarce in the NAC. Dense distribution of NT- and SP-containing fibers or puncta were observed in the mediodorsal part (medial subdivision), where a dense field of DA-immunoreactive fibers was observed. The ventral part (ventral subdivision) contained moderate numbers of NT- and SP-immunoreactive fibers. Haloperidol-induced c-fos expression was very extensive in the medial half of NAC, particularly in the mediodorsal region, which overlapped with the DA- and peptide-rich region. The present study indicates that the NAC of the primate can be subdivided into at least three subterritories, the dorsolateral, medial and ventral subdivision, by neuropeptide histochemistry as well as by the response of its constituent neurons to haloperidol.

Animals↗
PubMed1995

Receptor mechanisms mediating clozapine-induced c-fos expression in the forebrain.

The atypical antipsychotic clozapine produces distinctly different regional patterns of c-fos expression in rat forebrain than does the prototypical neuroleptic haloperidol. While haloperidol-induced c-fos expression appears to be mediated by its D2 dopamine receptor antagonist properties, the mechanisms by which clozapine increases c-fos expression remain uncertain. Using a combination of brain lesion, pharmacological and immunohistochemical techniques, the present study sought to determine the receptor mechanisms by which clozapine increases the number of Fos-like immunoreactive neurons in various regions of the forebrain. To test whether serotonergic and/or noradrenergic systems are involved in clozapine-induced c-fos expression, rats received either 5,7-dihydroxytryptamine lesions of the medial forebrain bundle or 6-hydroxydopamine lesions of the dorsal noradrenergic bundle two weeks prior to clozapine (20 mg/kg) injections. Neither type of lesion affected clozapine-induced c-fos expression in the rat forebrain, suggesting that neither serotonergic nor noradrenergic mechanisms are involved in this action of clozapine. In another experiment, the 5-hydroxytryptamine2 receptor antagonist ritanserin (5 mg/kg), either alone or in combination with haloperidol (1 mg/kg), failed to mimic the pattern of c-fos expression produced by clozapine. This suggests that clozapine's antagonist actions at 5-hydroxytryptamine2 receptors cannot explain the unique pattern of regional c-fos expression produced by this compound. To determine whether the blockade of subtypes of the D2 dopamine receptor family may contribute to clozapine's effects, the dopamine receptor agonists quinpirole and 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) were injected 15 min prior to clozapine. Quinpirole produced a small but significant decrease in clozapine-induced c-fos expression in the medial prefrontal cortex, had larger effects in the lateral septum, and blocked clozapine's actions in the nucleus accumbens and major island of Calleja. Pretreatment with 7-OH-DPAT attenuated clozapine-induced c-fos expression in the nucleus accumbens and lateral septum, completely blocked the expression in the major island of Calleja, but was without effect in the medial prefrontal cortex. Given the different affinities of quinpirole and 7-OH-DPAT for D2, D3 and D4 receptors, these data suggest that clozapine-induced increases in c-fos expression in the nucleus accumbens, major island of Cajella and lateral septal nucleus are due to antagonist actions of this antipsychotic at D3 dopamine receptors. They also indicate that while antagonist actions at D4 receptors may contribute, the primary mechanisms by which clozapine increases c-fos expression in the medial prefrontal cortex remain to be determined.

Animals↗
PubMed1995

Increases in hippocampal and frontal cortical acetylcholine release associated with presentation of sensory stimuli.

In vivo microdialysis was employed to monitor acetylcholine release in the hippocampus and frontal cortex of freely behaving rats. Four stimuli were presented on separate occasions in the course of a dialysis session to rats with microdialysis probes implanted in the hippocampus or frontal cortex. Visual, auditory, olfactory and tactile stimuli elicited a number of different responses such as exploratory and consummatory behaviours. Presentation of two of the stimuli (auditory and tactile) also produced periods of alert immobility (freezing). All of the stimuli increased acetylcholine release in both the hippocampus and cortex: in the hippocampus, this increase was statistically significant with all except the olfactory stimulus, whereas in the cortex all but the visual stimulus resulted in significant increases. In the hippocampus, there were no significant differences between the increases in acetylcholine release produced by the four stimuli. In contrast, in the cortex, there was significant variation between the magnitude of acetylcholine release produced by the different stimuli: acetylcholine release elicited by tactile stimulation was greater than that produced by the other stimuli. There was no significant variation in the duration of increases in acetylcholine release produced by the stimuli in either the hippocampus or cortex. These results provide evidence that acetylcholine release is associated with a variety of behavioural responses to stimuli designed to produce arousal, and point to a role for cortical and hippocampal cholinergic mechanisms in arousal or attention. Further, the results suggest that under some circumstances cortical and hippocampal acetylcholine release may be regulated differentially.

Acetylcholine↗
PubMed1995

Serotonergic regulation of acetylcholine release in rat frontal cortex.

The extent to which serotonin regulates the activity of cortically projecting cholinergic neurons was studied using in vivo microdialysis to monitor interstitial concentrations of acetylcholine in the frontal cortex of freely moving rats. Systemic administration of the serotonin release-inducing agent fenfluramine (3 or 10 mg/kg, i.p.) increased acetylcholine release by 110-130%. The fenfluramine-induced increase in acetylcholine release was significantly attenuated by pretreatment with the selective serotonin uptake inhibitor fluoxetine (10 mg/kg, i.p.). Pretreatment with the selective dopamine D1 receptor antagonist SCH-23390 (0.3 mg/kg, s.c.) failed to prevent the fenfluramine-induced increase in acetylcholine release. In contrast, the serotonin 5-HT2A receptor antagonist ketanserin (5 mg/kg, i.p.) blocked fenfluramine-induced increases in acetylcholine release. In contrast to previous studies that have concluded that serotonin has inhibitory actions on cortical acetylcholine release, the present results indicate that fenfluramine increases cortical acetylcholine release in vivo by its ability to enhance serotonin transmission and that serotonin produces these effects at least in part via actions at serotonin 5-HT2A receptors.

Acetylcholine↗
PubMed1995

Cortical regulation of subcortical dopamine release: mediation via the ventral tegmental area.

In vivo microdialysis was used to determine the extent to which ionotropic glutamate receptors in the ventral tegmental area (VTA) regulate dopamine release in the nucleus accumbens. Coapplication of 2-amino-5-phosphonopentanoic acid (AP5; 200 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 50 microM) to the VTA via reverse dialysis decreased extracellular concentrations of dopamine in the nucleus accumbens by approximately 30%. In accordance with previous results, electrical stimulation of the prefrontal cortex increased dopamine release by 60%. Application of AP5 and CNQX to the VTA during cortical stimulation blocked the effect of stimulation on dopamine release. These results indicate that ionotropic glutamate receptors in the VTA are critically involved in basal and evoked dopamine release in the nucleus accumbens and suggest that a glutamatergic projection from the prefrontal cortex regulates the activity of dopaminergic neurons in the VTA.

2-Amino-5-phosphonovalerate↗
PubMed1995

Dopaminergic correlates of motivated behavior: importance of drive.

In vivo brain microdialysis was used to monitor changes in dopamine (DA) release in the nucleus accumbens (NAc) during anticipatory and consummatory components of feeding behavior. During 10 daily training sessions, rats were first confined to one compartment of a testing chamber for 10 minutes. During this period (anticipatory phase) they were prevented from gaining access to a highly palatable liquid meal by a wire mesh screen. The screen was then removed and the animals were permitted to consume the meal for 20 min (consummatory phase). On removal of the screen, the latency to begin drinking decreased and the amount consumed increased as a function of days of training, both measures reaching asymptotic levels by day 7. Trained animals were implanted with dialysis probes in the NAc on day 10, and on day 12 DA release was monitored during the feeding session. Compared to controls, trained animals failed to show significantly greater increases in accumbal DA release during the anticipatory phase, all groups showing small (approximately 10%) increases on being placed in the test chamber. In contrast, compared to controls, DA release increased significantly in the NAc during consumption of the palatable meal. The magnitude of this increase was significantly enhanced (30% vs 71% peak increase) in animals that were 20 hr food deprived at the time of testing. The latter animals also showed a statistically significant increase (24%) in DA release during the anticipatory phase. A subsequent experiment in which consumption of the palatable liquid was limited to 5 ml in deprived and nondeprived animals indicated that only part of the deprivation-induced potentiation of accumbal DA release could be attributed to the larger volume consumed by the deprived animals. That is, the same volume and rate of consumption of a small amount of the liquid diet produced a significantly greater increase in accumbal DA release in deprived than in nondeprived animals (42% vs 23% peak increase). Feeding-induced increases in accumbal DA release were not due to postingestional factors as direct injections of the liquid diet into the stomach by gavage failed to produce this effect. The results of these experiments indicate (1) that consummatory rather than anticipatory aspects of feeding are robustly associated with increases in DA release in the NAc, and (2) that motivational state can influence the magnitude of the neurochemical events that are associated with goal-directed behaviors.

Animals↗
PubMed1995

Bupropion: a review of its mechanism of antidepressant activity.

BACKGROUND: The mechanism of action of the novel antidepressant bupropion remains unclear after many years of study. A review of the relevant biochemical, in vivo brain microdialysis, electrophysiologic, behavioral, and clinical data clarifies what is known about this unique compound and suggests possible modes of action. METHOD: A panel of 11 experts was convened for a conference to discuss bupropion's mechanism of antidepressant activity. Four of the panelists presented current research findings, followed by a discussion. RESULTS: (1) Biochemical studies suggest down-regulation of postsynaptic beta-adrenoceptors and desensitization of the norepinephrine-stimulated adenylate cyclase in the rat cortex occur only after chronic administration of very high doses of bupropion. (2) In vivo brain microdialysis studies demonstrate that, after chronic administration, there is an enhancement of bupropion-induced increases in extracellular dopamine in the nucleus accumbens. (3) Electrophysiologic data show that with acute dosing, bupropion reduces the firing rates of noradrenergic neurons in the locus ceruleus. The firing rates of dopaminergic neurons are reduced by bupropion in the A9 and A10 areas of the brain, but only at very high doses, and bupropion does not alter the firing rates of serotonergic neurons in the dorsal raphe. (4) Behavioral studies show that the most active metabolite of bupropion, hydroxybupropion (306U73), appears to be responsible for a large part of the compound's effects in animal models of antidepressant activity. (5) Clinical studies indicate that bupropion enhances noradrenergic functional activity as reflected by an increased excretion of the hydroxy metabolite of melatonin, while at the same time producing a presumably compensatory decrease in norepinephrine turnover. In one study, bupropion elevated plasma levels of the dopamine metabolite homovanillic acid in nonresponders, but not in responders. CONCLUSION: The mechanism of action of bupropion appears to have an unusual, not fully understood, noradrenergic link. The bupropion metabolite hydroxybupropion probably plays a critical role in bupropion's antidepressant activity, which appears to be predominantly associated with long-term noradrenergic effects. The mild central nervous system activating effects of bupropion appear to be due to weak dopaminergic mechanisms. There is some evidence that dopamine may contribute to bupropion's antidepressant properties. Antidepressant effects of bupropion are not serotonergically mediated.

Animals↗
PubMed1995

Electrical stimulation of the prefrontal cortex increases dopamine release in the nucleus accumbens of the rat: modulation by metabotropic glutamate receptors.

In vivo microdialysis was used to assess the effects of electrical stimulation of the prefrontal cortex (PFC) on dopamine (DA) release in the nucleus accumbens (NAC) of awake, unrestrained rats. The PFC was stimulated bilaterally for 20 min at parameters previously shown to support intracranial self-stimulation in this structure. Stimulation at 50 microA evoked a 38% increase in DA release while 100 microA produced a 69% increase. Thus, phasic activation of the PFC increases DA release in the NAC. Additional experiments were performed to establish whether glutamate receptors in the NAC mediated these effects. The noncompetitive NMDA antagonist dizocilpine maleate (MK-801) and the broad spectrum competitive antagonist kynurenic acid were each applied locally to the NAC via reverse dialysis alone or in combination with electrical stimulation of the PFC (100 microA). Both MK-801 (10 microM) and kynurenic acid (5 mM) increased DA release when administered alone. When a "subthreshold" concentration (i.e., the highest concentration employed that did not itself increase DA release) of either compound was administered together with PFC stimulation, neither kynurenic acid (1 mM) nor MK-801 (1 microM) attenuated the effect of stimulation on DA release, thereby indicating that this effect is not mediated by ionotropic glutamate receptors located within the NAC. To examine the possible role of metabotropic glutamate receptors in regulating DA release, the metabotropic glutamate agonist trans(1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) was employed. When applied locally to the NAC, ACPD had a dose-dependent effect on DA release with a high concentration (1 mM) causing an increase and a lower concentration (100 microM) causing a small decrease.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Conditioned fear-induced changes in behavior and in the expression of the immediate early gene c-fos: with and without diazepam pretreatment.

The synthesis of Fos, the protein product of the immediate early gene c-fos, was used to map metabolically some of the neural substrates of conditioned fear in the rat. Analysis of the behaviors emitted by the rats during the test session provided strong evidence that the conditioning procedure was effective. Exposure to the environment in which they had previously received footshock significantly increased the number of Fos-like immunoreactive neurons in nearly 50 brain regions, both cortical and subcortical. Among the structures showing the most dramatic increases in fear-induced c-fos expression were the cingulate, piriform, infralimbic, and retrosplenial cortices, the anterior olfactory nucleus, claustrum, endopiriform nucleus, nucleus accumbens shell, lateral septal nucleus, various amygdalar nuclei, paraventricular thalamic nucleus, ventral lateral geniculate nucleus, the ventromedial, lateral, and dorsal hypothalamic nuclei, the ventral tegmental area, and the supramammillary area. These data demonstrate that a relatively simple classical conditioning procedure activates a large number of widely dispersed cortical and subcortical structures. Some of the structures showing increased c-fos expression have important autonomic functions and may therefore have reflected centrally mediated changes in blood pressure and respiration produced by the anxiogenic stimuli. In a second experiment, the effects of pretreatment with the anxiolytic drug diazepam (2.5, 5.0, or 10 mg/kg) were evaluated. The benzodiazepine produced dose-related decreases in the frequency of crouching (freezing) elicited by the aversively conditioned contextual cues. Diazepam also produced dose-related decreases in conditioned stress-induced c-fos expression in all but one structure, the effects being statistically significant in 38 of 60 sampled structures. Diazepam dose dependently increased fear-induced c-fos expression in the central nucleus of the amygdala. There was considerable regional variability with respect to sensitivity to diazepam, the retrosplenial cortex and the supramammillary area being the only two structures to show decreases after the lowest dose of diazepam. In contrast, the entorhinal cortex, nucleus accumbens core, ventromedial and posterior hypothalamic nuclei, median raphe, and locus coeruleus were particularly resistant to diazepam, all failing to show statistically significant decreases in conditioned fear-induced c-fos expression even at the highest dose. The extent to which diazepam decreased conditioned stress-induced c-fos expression was unrelated to previous estimates of benzodiazepine receptor density in the sampled structures.

Animals↗
PubMed1994

Electroconvulsive shock increases interstitial concentrations of uric acid in the rat brain.

This study examined the effects of electroconvulsive shock (ECS) on striatal interstitial concentrations of the purine metabolite uric acid (UA) using microdialysis in freely moving rats. UA increased to about 200% of baseline following ECS. Intense seizure activity induced by the convulsant agent flurothyl also resulted in a two-fold increase of UA concentrations suggesting that the ECS-induced UA increase is related to the seizure activity per se. Local administration of tetrodotoxin or perfusion with a Ca(2+)-free solution failed to affect the basal or the ECS-induced increase in UA concentrations. These data indicate that both the basal and the stimulated interstitial concentrations of uric acid are not dependent upon neuronal activity and exocytotic release. The UA response to ECS appears to be refractory to a second ECS delivered 2 but not 24 h after the first. Intrastriatal infusion of allopurinol (1 mM), an inhibitor of UA synthesis, decreased basal UA concentrations to 26% but did not influence the ECS-induced UA increase. Systemic injection of allopurinol (20 mg/kg, i.p.) decreased basal UA concentrations to 25% and prevented the ECS-induced UA elevation. ECS also increased serum concentrations of UA to almost 200% of baseline. Allopurinol (20 mg/kg, i.p.) markedly decreased serum UA concentrations to non-detectable levels and completely abolished the ECS-induced increase. The estimated concentration difference between blood and brain interstitial UA strongly suggests that ECS-induced increase in brain interstitial UA concentrations is of peripheral origin possibly due to disruption of the blood brain barrier during seizure activity.

Administration, Topical↗
PubMed1994

Dopamine depletion attenuates amphetamine-induced increases of cortical acetylcholine release.

The extent to which the d-amphetamine (2.0 mg/kg)-induced increase in cortical acetylcholine release is mediated by dopamine and/or noradrenaline was assessed using in vivo microdialysis in freely moving rats. Unilateral 6-hydroxydopamine lesions of the mesotelencephalic dopaminergic system, which depleted forebrain dopamine by 99% on the lesioned side, significantly attenuated the effect of d-amphetamine on cortical acetylcholine release compared to a surgical control group (160% baseline vs. 270%), suggesting that dopamine at least in part mediates this effect of d-amphetamine. In contrast, bilateral 6-hydroxydopamine lesions of the dorsal noradrenergic bundle which depleted forebrain noradrenaline by at least 95% had no effect on d-amphetamine-stimulated cortical acetylcholine release. These results point to an important role for forebrain dopamine in the regulation of cortically projecting cholinergic neurons and fail to support the hypothesis that the ascending noradrenergic projections of the locus coeruleus are significantly involved.

Acetylcholine↗
PubMed1994

The potent and selective dopamine D1 receptor agonist A-77636 increases cortical and hippocampal acetylcholine release in the rat.

The effects of systemic administration of the full dopamine D1 receptor agonist A-77636 on acetylcholine release in rat frontal cortex and hippocampus were studied using in vivo microdialysis. Administration of A-77636 (4 mumol/kg s.c.) greatly (> 230%) increased both cortical and hippocampal acetylcholine release for more than 3 h; at a lower dose (1 mumol/kg s.c.) A-77636 significantly stimulated cortical but not hippocampal acetylcholine release. The effect of the higher dose of A-77636 on cortical acetylcholine release was blocked by the dopamine D1 receptor antagonist SCH 23390 (300 micrograms/kg s.c.). These results confirm that stimulation of dopamine D1 receptors facilitates cortical and hippocampal acetylcholine release in vivo, and indicate that these two structures are differentially sensitive to this effect. They also raise the possibility that dopamine D1 receptor agonists may be useful in the treatment of cortical and hippocampal acetylcholine deficit-related syndromes.

Acetylcholine↗
PubMed1994

Cortical regulation of acetylcholine release in rat striatum.

The effect of electrical stimulation of the prefrontal cortex (PFC) on acetylcholine (ACh) release in the dorsal striatum was investigated using on line in vivo microdialysis. ACh output was sampled before, during and after 20-min periods of 50 and 100 microA stimulation in awake, unrestrained rats. Both currents increased extracellular ACh by approximately 30% above baseline. ACh concentrations reached their maximum values during the last 10 min of the stimulation period and returned to baseline within 20 min. These results provide direct functional evidence for cortical modulation of cholinergic interneurons in the striatum.

Acetylcholine↗
PubMed1994

Enhanced acetylcholine release in hippocampus and cortex during the anticipation and consumption of a palatable meal.

In rats trained for 14 days to consume a palatable liquid chocolate meal (Sustacal), in vivo brain microdialysis was used to measure release of acetylcholine in the frontal cortex and hippocampus during anticipation and consumption of the meal. Rats were trained in an experimental chamber in which they were separated from the Sustacal by a screen for 20 min (trained, rewarded group). The screen was then removed and the rats were allowed 20 min of access to the meal. Two control groups were run concurrently: these groups consisted of rats (i) that were trained over 14 days but only had access to water in the experimental chamber (trained, non-rewarded), or (ii) that were introduced into the experimental chamber for the first time on the final test (i.e. dialysis) session, and presented with Sustacal (naive). Different results were obtained in the hippocampus and frontal cortex. In the hippocampus there were no group differences with respect to acetylcholine release. Thus, in all three groups acetylcholine release increased to about 220% of basal values when animals were placed in the experimental chamber. In the frontal cortex, acetylcholine release also increased significantly in all three groups. However, the extent of this increase was significantly greater in the trained, rewarded group, reaching approximately 300% of basal values during the anticipatory and consummatory components of the task. The significant increases in acetylcholine release which occurred in both the hippocampus and frontal cortex of each of the three groups are consistent with an involvement of cholinergic basal forebrain neurons in the regulation of arousal or attention. In addition, however, acetylcholine release in the frontal cortex can be further selectively enhanced by the animal's past training experience, perhaps being associated with the anticipation of reward.

Acetylcholine↗
PubMed1994

Dopaminergic regulation of septohippocampal cholinergic neurons.

The extent to which acetylcholine (ACh) release in the hippocampus is regulated by dopaminergic mechanisms was assessed using in vivo microdialysis in freely moving rats. Systemic administration of the dopamine (DA) receptor agonist apomorphine (1.0 mg/kg) or the specific D1 agonist CY 208-243 (1.0 mg/kg) increased microdialysate concentrations of ACh in the hippocampus. The D2 receptor agonist quinpirole (0.5 mg/kg) produced a small but statistically significant decrease in hippocampal ACh release. d-Amphetamine (2.0 mg/kg) increased ACh release, an effect that was blocked by the D1 receptor antagonist SCH 23390 (0.3 mg/kg) but not by the D2 antagonist raclopride (1.0 mg/kg). These findings suggest that endogenous DA stimulates septohippocampal cholinergic neurons primarily via actions at D1 receptors. In addition, these results are similar to previous findings regarding the dopaminergic regulation of cortical ACh release, and suggest that the anatomical continuum formed by basal forebrain cholinergic neurons that project to the cortex and hippocampus acts as a functional unit, at least with respect to its regulation by DA.

Acetylcholine↗
PubMed1994

Neuroanatomical targets of neuroleptic drugs as revealed by Fos immunochemistry.

Many physiologic and pharmacologic stimuli rapidly increase the expression in the central nervous system of immediate early genes such as c-fos. Immunohistochemical mapping of the protein product of c-fos gene expression (Fos) can be used to identify some of the individual neurons whose activities have been altered by such stimuli. This brief review describes the use of this strategy in identifying potential neuroanatomical targets of neuroleptic drugs. Among the most significant findings to date is the demonstration by several laboratories that the regional pattern of clozapine-induced c-fos expression differs significantly from that produced by typical neuroleptics such as haloperidol. Fos immunohistochemistry may be a rapid and reliable method for identifying new antipsychotic drugs that have a broader spectrum of therapeutic activity and reduced liabilities for producing extrapyramidal side effects.

Animals↗