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PubMed2002

Prefrontal cortex acetylcholine release, EEG slow waves, and spindles are modulated by M2 autoreceptors in C57BL/6J mouse.

Recent evidence suggests that muscarinic cholinergic receptors of the M2 subtype serve as autoreceptors modulating acetylcholine (ACh) release in prefrontal cortex. The potential contribution of M2 autoreceptors to excitability control of prefrontal cortex has not been investigated. The present study tested the hypothesis that M2 autoreceptors contribute to activation of the cortical electroencephalogram (EEG) in C57BL/6J (B6) mouse. This hypothesis was evaluated using microdialysis delivery of the muscarinic antagonist AF-DX116 (3 nM) while simultaneously quantifying ACh release in prefrontal cortex, number of 7- to 14-Hz EEG spindles, and EEG power spectral density. Mean ACh release in prefrontal cortex was significantly increased (P < 0.0002) by AF-DX116. The number of 7- to 14-Hz EEG spindles caused by halothane anesthesia was significantly decreased (P < 0.0001) by dialysis delivery of AF-DX116 to prefrontal cortex. The cholinergically induced cortical activation was characterized by a significant (P < 0.05) decrease in slow-wave EEG power. Together, these neurochemical and EEG data support the conclusion that M2 autoreceptor enhancement of ACh release in prefrontal cortex activates EEG in contralateral prefrontal cortex of B6 mouse. EEG slow-wave activity varies across mouse strains, and the results encourage comparative phenotyping of cortical ACh release and EEG in additional mouse models.

Acetylcholine↗
PubMed1989

Retrospective and prospective coding of information: role of the medial prefrontal cortex.

Animals with sham-operations or medial prefrontal cortex lesions were trained in a task which required memory for short or long lists of items (spatial locations). On any one trial a rat is presented with 2, 4, 6, 8 or 10 items (spatial locations) on a 12-arm radial maze followed 15 min later by a win-shift test comprising a choice between a place previously visited and a novel place. Sham-operated animals showed an increase in errors as a function of set size (2 to 8 items) followed by a decrease in errors with a set size of 10 items suggesting the use of both retrospective and prospective memory codes. In contrast, animals with medial prefrontal cortex lesions made most of their errors for the longest list length reflecting an inability to shift from a retrospective to prospective memory code. The results are interpreted as support for a medial prefrontal cortex role in mediating a prospective code perhaps via knowledge systems based on temporal information.

Animals↗
PubMed1999

Medial prefrontal cortex depressor response: role of the solitary tract nucleus in the rat.

The depressor response elicited by unilateral low intensity electrical stimulation of the rat ventral medial prefrontal cortex may be mediated by a connection with the solitary tract nucleus. We tested this hypothesis by (i) examining the influence of medial prefrontal cortex stimulation on the induction of Fos-like immunoreactivity in neurons in the medulla oblongata, and (ii) by testing the effect of inhibition of solitary tract nucleus neurons on the medial prefrontal cortex stimulation-evoked depressor response. Depressor responses (>10 mmHg) were elicited by electrical stimulation of the medial prefrontal cortex every minute for 1 h ('Stimulated' group). Control animals were treated identically but did not receive electrical stimulation ('Unstimulated' group). Neurons exhibiting Fos-like immunoreactivity were abundant at the stimulation site which included the infralimbic area, and dorsal peduncular cortex. Medullary Fos-like immunoreactivity observed in the 'Stimulated' and 'Unstimulated' groups exceeded levels observed in untreated rats and was detected in the rostral, caudal and intermediate areas of the ventrolateral medulla, and the commissural, intermediate, medial and lateral regions of the solitary tract nucleus, as well as the medial vestibular nucleus, and the dorsal motor nucleus of the vagus. The number of neurons displaying Fos-like immunoreactivity in the ipsilateral solitary tract nucleus and caudal ventrolateral medulla of the 'Stimulated' group was found to be significantly elevated compared to the contralateral side (P<0.05), and the 'Unstimulated' group bilaterally. Inhibition of solitary tract nucleus neurons using bilateral injections of the GABA(A) receptor agonist muscimol (44 pmol/25 nl) inhibited the sympathetic vasomotor baroreflex and attenuated the depressor and sympathoinhibitory response to medial prefrontal cortex stimulation by 62% and 65%, respectively. These findings suggest that the projection from the medial prefrontal cortex to the solitary tract nucleus is excitatory and support the hypothesis that the depressor response elicited by medial prefrontal cortex stimulation is mediated, in part, by a cortico-solitary projection which activates the intramedullary baroreflex pathway.

Animals↗
PubMedDate not supplied

Protective effects of omega-3 essential fatty acids against formaldehyde-induced neuronal damage in prefrontal cortex of rats.

The aim of this study was to examine the neurotoxicity of formaldehyde on prefrontal cortex and the protective effects of omega-3 essential fatty acids against these toxic effects. For this purpose, 21 male Wistar rats were divided into three groups. The rats in group I comprised the controls, while the rats in group II were injected every other day with formaldehyde (FA). The rats in group III received omega-3 fatty acids daily while exposed to formaldehyde. At the end of the 14-day experimental period, all rats were killed by decapitation. The brains of the rats were removed and the prefrontal cortex tissues were obtained from all brain specimens. Some of the prefrontal cortex tissue specimens were used for determination of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels. The remaining prefrontal cortex tissue specimens were used for light microscopic and immunohistochemical evaluation. The levels of SOD and GSH-Px were significantly decreased, and MDA levels were significantly increased in rats treated with formaldehyde compared with those of the controls. Furthermore, in the microscopic examination of this group, formation of apoptotic bodies, pycnotic cells, and apoptotic cells including nuclear fragmentation and membrane budding were observed. However, increased SOD and GSH-Px enzyme activities, and decreased MDA levels were detected in the rats administered omega-3 fatty acids while exposed to formaldehyde. Additionally, cellular damage caused by formaldehyde was decreased, and structural appearance was similar to that of the control rats in this group. The biochemical and histological findings observed in all groups were also confirmed by immunohistochemical evaluation. It was determined that formaldehyde-induced neuronal damage in prefrontal cortex was prevented by administration of omega-3 essential fatty acids.

Animals↗
PubMed1984

Inhibitory influence of the mesocortical dopaminergic system on spontaneous activity or excitatory response induced from the thalamic mediodorsal nucleus in the rat medial prefrontal cortex.

Since the medial prefrontal cortex receives converging projections from the mediodorsal nucleus of the thalamus (MD) and the dopaminergic neurons located in the ventromedial mesenscephalic tegmentum (VMT) the responses of cortical neurons to ipsilateral VMT and MD stimulation (50-150 microA; 0.2-0.5 ms duration) were analyzed in ketamine anaesthetized rats. MD stimulation at 1 Hz blocked the firing of 99% of the spontaneously active cortical units tested (mean latency, 15 ms; mean duration, 182 ms). MD stimulation at 5-10 Hz evoked single spike responses (mean latency, 16 ms) in 80% of the units tested. Ten to 15 days after kainic acid injection into the MD the number of cortical neurons inhibited (1 Hz) or excitated (5-10 Hz was reduced to 57 and 18%, respectively. Following stimulation of the VMT (at a frequency of 1-5 Hz), 85% of cortical neurons showed an arrest of spontaneous firing occurring after a mean latency of 17 ms and lasting 109 ms on the average. Most of the cells displaying the VMT inhibitory effect were excitated by MD stimulation. Moreover VMT stimulation, applied 3-45 ms before that of MD, blocked the excitation induced by MD in 75% of the units tested. After injection of 6-hydroxydopamine into the medial forebrain bundle or intraperitoneal administration of alpha-methyl-paratyrosine (alpha-MpT), the number of units tested responding to VMT stimulation was of 19 and 35%, respectively. Moreover in these treated rats, the proportion of excitatory responses to MD blocked by VMT stimulation was reduced to 5 and 6%.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1997

The course of neural projection from the prefrontal cortex to the nucleus accumbens in the rat.

Corticostriatal neurons linking the prefrontal cortex and the nucleus accumbens connect the terminal fields of the ascending mesotelencephalic dopamine neurons and may potentially mediate cortical dopaminergic modulation of subcortical dopamine transmission. In our attempt to develop a brain slice preparation that maximally preserves this prefrontal accumbens pathway for in vitro electrophysiological studies, knowledge of the complete course of its projection is critical. Microinjection of biotin-dextran amine as an anterograde tracer into the prefrontal cortex revealed the following in the coronal, sagittal and oblique planes of rat brain. (1) Axonal fibers from the rostral prelimbic cortex projected at an angle of approximately 60 degrees to the horizontal plane through the infralimbic region and mainly entered the rostromedial accumbens. Some also chose a ventral route to enter the "core" of the accumbens. (2) From the central ventral prelimbic regions, axons spread out diffusely and descended to the dorsal accumbens. They then entered throughout the rostral-caudal "shell" of the nucleus accumbens. (3) From the caudal prelimbic region of the prefrontal cortex, axonal fibers descended approximately 10 degrees to the coronal plane and entered the dorsal nucleus accumbens and the caudate nucleus. The denser caudate-projecting fibers gave rise to collaterals that entered the accumbens "core". These results suggest that brain slices that preserve the rostral prelimbic-medial accumbens pathway can be obtained by an oblique (approximately 60 degrees) cut, whereas preservation of the caudal prefrontal-accumbens neurons necessitates a 10 degrees cut. Finally, in whole-cell patch-clamp recordings of accumbens neurons in such slices, orthodromically evoked excitatory postsynaptic potentials to deep layer prefrontal cortical stimulation were observed, thus confirming the functional preservation of portions of this prefrontal cortex nucleus accumbens pathway.

Animals↗
PubMed1992

Dopamine and the neural circuitry of primate prefrontal cortex: implications for schizophrenia research.

Dopaminergic systems have been implicated in the pathophysiology of schizophrenia; the prefrontal cortex may be a site of dysfunction in this disorder. Until recently, however, relatively little was known about the organization of dopaminergic afferents, or the relationship of those axons to other elements of neural circuitry in the expanded and highly differentiated prefrontal cortex of primates. In this paper we review recent studies demonstrating that monkey prefrontal cortex is innervated by dopaminergic axons in a highly specific regional and laminar fashion. These findings are considered in the context of the organization of other neural systems in monkey prefrontal cortex and with regard to the extent to which they represent the organization of human prefrontal cortex. The resulting model of prefrontal cortical circuitry is then discussed in terms of the ways in which that circuitry might be disrupted in schizophrenia.

Animals↗
PubMed2004

Chronic stress alters dendritic morphology in rat medial prefrontal cortex.

Chronic stress produces deficits in cognition accompanied by alterations in neural chemistry and morphology. Medial prefrontal cortex is a target for glucocorticoids involved in the stress response. We have previously demonstrated that 3 weeks of daily corticosterone injections result in dendritic reorganization in pyramidal neurons in layer II-III of medial prefrontal cortex. To determine if similar morphological changes occur in response to chronic stress, we assessed the effects of daily restraint stress on dendritic morphology in medial prefrontal cortex. Male rats were exposed to either 3 h of restraint stress daily for 3 weeks or left unhandled except for weighing during this period. On the last day of restraint, animals were overdosed and brains were stained using a Golgi-Cox procedure. Pyramidal neurons in lamina II-III of medial prefrontal cortex were drawn in three dimensions, and the morphology of apical and basilar arbors was quantified. Sholl analyses demonstrated a significant alteration of apical dendrites in stressed animals: overall, the number and length of apical dendritic branches was reduced by 18 and 32%, respectively. The reduction in apical dendritic arbor was restricted to distal and higher-order branches, and may reflect atrophy of terminal branches: terminal branch number and length were reduced by 19 and 35%. On the other hand, basilar dendrites were not affected. This pattern of dendritic reorganization is similar to that seen after daily corticosterone injections. This reorganization likely reflects functional changes in prefrontal cortex and may contribute to stress-induced changes in cognition.

Animals↗
PubMed1984

Dual pathways connecting the dorsolateral prefrontal cortex with the hippocampal formation and parahippocampal cortex in the rhesus monkey.

Anterograde and retrograde tracing methods including autoradiography, horseradish peroxidase histochemistry and fluorescent dye transport were used to demonstrate that the dorsolateral prefrontal cortex is connected with the hippocampal formation and associated cortical regions by two distinct pathways. Fibers forming a lateral pathway travel in the fronto-occipital fasciculus and connect the dorsolateral prefrontal cortex with the fundus of the rhinal sulcus, posterior subdivisions of the parahippocampal gyrus, and the presubiculum. A larger medial pathway forms in the cingulum bundle and terminates in the most caudal part of the presubiculum, as well as in adjacent transitional cortices. These cortices form a caudomedial promontory that is located between the posterior cingulate and prestriate areas. In all allo- and mesocortical targets of prefrontal cortex, labeled terminals form banding patterns reminiscent of the columnar organization of afferent fiber columns in neocortex. The same cytoarchitectonic areas that receive prefrontal afferents issue reciprocal projections. The largest source is the caudomedial lobule including its presubicular portion. Neurons in the parahippocampal gyrus and adjacent presubiculum also are retrogradely labeled following implants of horseradish peroxidase or injection of fluorescent dyes into prefrontal cortex. In addition, subicular neurons project to the prefrontal cortex although the subiculum does not appear to receive prefrontal afferent input. These findings emphasize that multiple channels of communication link the dorsolateral prefrontal cortex and the hippocampus via the parahippocampal gyrus, subiculum, presubiculum and adjacent transitional cortices. We speculate that each of these prefrontal projections may carry highly specific information into the hippocampus, whereas the reciprocal projections may allow retrieval by prefrontal cortex of memories stored in the hippocampus.

Animals↗
PubMed1997

Loss of dopamine terminals in the medial prefrontal cortex increased the ratio of DOPAC to DA in tissue of the nucleus accumbens shell: role of stress.

We examined whether dopamine depletion in the medial prefrontal cortex of the rat differentially affects basal and evoked dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) content in the subareas of the neostriatum and nucleus accumbens. Loss of approximately 80% of tissue dopamine content in the medial prefrontal cortex did not significantly alter basal tissue concentrations of dopamine or DOPAC or the DOPAC:dopamine ratio in either the nucleus accumbens core or shell or the medial or lateral neostriatum. However, tail pressure stress significantly increased the DOPAC:dopamine ratio in the nucleus accumbens shell of lesioned rats. Because dorsal and ventral areas of the medial prefrontal cortex preferentially innervate the core and shell, respectively, we sought to determine whether the selective effect of lesions on dopamine terminals in the shell of the nucleus accumbens are paralleled by greater dopamine loss in the ventral medial prefrontal cortex. 6-Hydroxydopamine decreased tissue concentrations of dopamine in both the dorsal (-74%) and ventral medial prefrontal cortex (-68%). In lesioned rats, few tyrosine hydroxylase-immunoreactive fibers remained in the dorsal medial prefrontal cortex whereas a dense innervation remained in the ventralmost area. The present data suggest that the influence of mesocortical dopamine neurons on the dopamine projection to the nucleus accumbens shell is expressed only under conditions of stress. Furthermore, lesion-induced alterations in dopamine neurons projecting to the nucleus accumbens shell are not due to a more extensive loss of dopamine terminals in the ventral than in the dorsal medial prefrontal cortex.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2000

Normal cellular levels of synaptophysin mRNA expression in the prefrontal cortex of subjects with schizophrenia.

BACKGROUND: Previous studies have reported that the 38-kd synaptic vesicle-associated protein, synaptophysin, is decreased in the prefrontal cortex of subjects with schizophrenia. METHODS: To determine whether the decreased protein levels reflect diminished expression of the synaptophysin gene by prefrontal cortex neurons, we used in situ hybridization histochemistry to determine the cellular levels of synaptophysin messenger RNA in prefrontal cortex area 9 from 10 matched pairs of schizophrenic and normal control subjects. RESULTS: Neither the density of neurons with detectable levels of synaptophysin messenger RNA nor the mean level of synaptophysin messenger RNA expression per neuron differed between schizophrenic and control subjects in any cortical layer. CONCLUSIONS: These findings indicate that the expression of synaptophysin messenger RNA is not altered in this brain region in schizophrenia. Consequently, reduced levels of synaptophysin protein in the prefrontal cortex of subjects with schizophrenia are more likely to reflect either posttranscriptional abnormalities of synaptophysin in prefrontal cortex neurons or a diminished number of axonal projections to the prefrontal cortex from other brain regions.

Adult↗
PubMed2002

Fluoxetine, but not other selective serotonin uptake inhibitors, increases norepinephrine and dopamine extracellular levels in prefrontal cortex.

RATIONALE: The selective serotonin uptake inhibitor (SSRI) fluoxetine has been shown to not only increase the extracellular concentrations of serotonin, but also dopamine and norepinephrine extracellular concentrations in rat prefrontal cortex. The effect of other SSRIs on monoamine concentrations in prefrontal cortex has not been thoroughly studied. OBJECTIVE: The aim of this study was to compare the ability of five systemically administered selective serotonin uptake inhibitors to increase acutely the extracellular concentrations of serotonin, norepinephrine and dopamine in rat prefrontal cortex. METHODS: The extracellular concentrations of monoamines were determined in the prefrontal cortex of conscious rats using the microdialysis technique. RESULTS: Fluoxetine, citalopram, fluvoxamine, paroxetine and sertraline similarly increased the extracellular concentrations of serotonin from 2- to 4-fold above baseline. However, only fluoxetine produced robust and sustained increases in extracellular concentrations of norepinephrine and dopamine after acute systemic administration. Fluoxetine at the same dose blocked ex vivo binding to the serotonin transporter, but not the norepinephrine transporter, suggesting that the increase of catecholamines was not due to non-selective blockade of norepinephrine uptake. Prefrontal cortex extracellular concentrations of fluoxetine at the dose that increased extracellular monoamines were 242 nM, a concentration sufficient to block 5-HT(2C) receptors which is a potential mechanism for the fluoxetine-induced increase in catecholamines. CONCLUSION: Amongst the SSRIs examined, only fluoxetine acutely increases extracellular concentrations of norepinephrine and dopamine as well as serotonin in prefrontal cortex, suggesting that fluoxetine is an atypical SSRI.

Animals↗
PubMed1982

Treatment with anticonvulsant drugs retards the development of brain-stimulation reward in the prefrontal cortex.

Electrical stimulation of the medial prefrontal cortex in rats daily for nine days caused a marked improvement in the rate of acquisition of a self-stimulation response. Diazepam (1 mg/kg, IP) or phenobarbital (15 mg/kg), but not phenytoin (25 mg/kg), administered during the nine day period of electrical stimulation, attenuated this facilitatory effect. However, diazepam or phenobarbital in the same dosages administered to self-stimulating rats (i.e., after acquisition) failed to alter responding. It was suggested that a kindling-like mechanism may underlie the development of self-stimulation of the prefrontal cortex.

Animals↗
PubMed2002

Volumetric reduction in left subgenual prefrontal cortex in early onset depression.

BACKGROUND: Subgenual prefrontal cortex (SGPFC) volume reduction has been reported in middle age adults with major depression (MD) or bipolar affective disorder. In this study, the authors test the hypothesis that SGPFC reduction is present in adolescent onset MD, and examine differences in the magnitude of reduction in younger versus older women. METHODS: Subgenual prefrontal cortex volume was measured from T1 weighted MR images in (1) 30 young women with early onset MD versus eight age-matched controls, and (2) 18 middle aged women with recurrent MD versus nine age-matched controls. RESULTS: Left SGPFC volume was reduced in adolescent and middle aged females with depression. The magnitude of the difference between depressed and control groups (average 19% difference) was similar in younger and older women. CONCLUSIONS: Left subgenual cingulate volume reductions are present in young women with adolescent onset MD.

Adolescent↗
PubMed1995

Hypofrontality does not occur with 6-hydroxydopamine lesions of the medial prefrontal cortex in rat brain.

This study examined the effect of lesions of dopamine (DA) nerve terminals the medial prefrontal cortex on local cerebral glucose utilization (LCGU) and dopamine metabolism in the rat brain. Bilateral 6-hydroxydopamine lesions were stereotaxically placed in the medial prefrontal cortex. Twenty-eight days after the lesion, concentrations of DA and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were determined in eight brain regions with a high-performance liquid chromatographic assay. LCGU was assessed by [14C]2-deoxy-D-glucose autoradiography. The lesion produced a striking reduction in DA (to 6% of the control value), and a moderate reduction in DOPAC and HVA in the medial prefrontal cortex. The ratio of DOPAC to DA in the medial prefrontal cortex was significantly elevated in the 6-OHDA lesioned animals. In contrast to DA depletion, LCGU in the medial prefrontal cortex of the lesioned rats was unaltered when compared with the control. These findings suggest that decreased energy metabolism in the frontal cortex, i.e., hypofrontality, does not occur with decreased DA innervation of that site.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Corticocortical projections to the prefrontal cortex in the rhesus monkey investigated with horseradish peroxidase techniques.

The corticocortical afferents innervating the prefrontal cortex in the monkey were studied by means of the retrograde axonal transport of horseradish peroxidase. After injection of small amounts (0.3-0.5 microliter) of this enzyme into various parts of the prefrontal cortex, many labeled neurons (mostly pyramids of 15-25 microns in diameter) were found in various cortical regions of the ipsilateral hemisphere. A small part of the prefrontal cortex received fibers from other parts of the same cortex. For example, area 8 receives many fibers from both the rostral part of area 9 and a small area adjacent to the inferior branch of the arcuate sulcus. On the other hand, area 9 in the inferior prefrontal convexity receives fibers from localized parts of areas 8 and 9 in the dorsolateral convexity as well as from area 6. It is also apparent that association connections from the dorsolateral to the inferior convexity are stronger than those going in the opposite direction. The prefrontal afferents from other cortical regions include many fibers originating from the posterior association cortex as well as some fibers arising in the cingulate and orbital gyri. The prefrontal cortex does not receive direct corticocortical fibers from the motor and "primary" sensory cortices. There is a topographic pattern in the prefrontal projections from the cortical walls (STs area) surrounding the superior temporal sulcus. Thus, the caudal half of the STs area projects to area 8 and a small adjacent part of area 9. The dorsal wall of the rostral half of the STs area projects to areas 9-12, the fundus to the inferior convexity, and the ventral wall only to the caudal part of the convexity. Projections from the circumjacent association cortex of the STs area to the prefrontal cortex as well as to the STs area are likewise found to be topographically organized. This suggests that certain parts of the posterior association cortex projecting to particular areas of the prefrontal cortex, also send fibers to those parts of the STs area which project to the same prefrontal areas.

Animals↗
PubMed1999

Effects of partial dopamine loss in the medial prefrontal cortex on local baseline and stress-evoked extracellular dopamine concentrations.

A reduction in the activity of mesoprefrontal dopamine neurons has been suggested to play a role in the pathophysiology of schizophrenia. Indeed, a recent study indicates that the density of tyrosine hydroxylase-immunoreactive axons is decreased in the deep layers of the prefrontal cortex of schizophrenic subjects [Akil et al., (1999) Am. J. Psychiatry, in press]. To determine the impact of partial loss of prefrontal dopamine axons on the activity of the remaining dopamine axons, we examined the effects of 6-hydroxydopamine lesions of the medial prefrontal cortex on local extracellular dopamine concentrations in the rat. In rats sustaining an average 63% loss of tyrosine hydroxylase-immunoreactive axons and no loss of dopamine-beta-hydroxylase-immunoreactive axons in the medial prefrontal cortex (smaller lesion), the baseline extracellular dopamine concentration was reduced by 63+/-9%. Thirty minutes of tail pressure increased extracellular dopamine in the medial prefrontal cortex by a maximum of 1.28+/-0.28 pg in control rats, but only 0.74+/-0.18 pg in rats with smaller lesions. In rats sustaining an average 80% loss of tyrosine hydroxylase-immunoreactive axons and 25% loss of dopamine-beta-hydroxylase-immunoreactive axons (larger lesion), the baseline extracellular dopamine concentration in the medial prefrontal cortex did not differ from control values. In addition, the maximum stress-evoked increase in dopamine concentration was also similar to that observed in control rats (+1.04+/-0.28 pg). The stress-induced increase in extracellular dopamine in the medial prefrontal cortex of rats sustaining smaller and larger lesions may occur in the absence of a corresponding increase in dopamine synthesis in mesoprefrontal dopamine neurons. This proposal is supported by our observation that stress did not alter tissue or extracellular 3,4-dihydroxyphenylacetic acid concentrations in the medial prefrontal cortex of lesioned rats. These data suggest that moderate loss of tyrosine hydroxylase-immunoreactive axons in the prefrontal cortex is sufficient to reduce extracellular dopamine concentrations in this brain region. In addition, a further reduction in tyrosine hydroxylase-immunoreactive axons in the medial prefrontal cortex, combined with the loss of dopamine-beta-hydroxylase-immunoreactive axons, results in normal extracellular dopamine concentrations in this area. We propose that the latter effect is due to increased neurochemical activity of remaining mesoprefrontal dopamine axons and/or decreased clearance of extracellular dopamine due to loss of both dopamine and norepinephrine transporters.

3,4-Dihydroxyphenylacetic Acid↗
PubMedDate not supplied

Multiple reward systems and the prefrontal cortex.

Electrical stimulation of the major divisions of the prefrontal cortex, the mediodorsal and sulcal areas, can serve as a reinforcing stimulus. Studies of self-stimulation of the prefrontal cortex have produced behavioral, anatomical and pharmacological evidence that the substrate of these rewarding effects can be dissociated from that subserving self-stimulation of ventral diencephalic sites such as the lateral hypothalamus. Other studies indicate that within the prefrontal cortex itself, self-stimulation of the medial and sulcal divisions can be attributed to dissociable processes. These observations suggest the existence of multiple, largely autonomous prefrontal subsystems involved in reinforcement. This raises the question of the functional significance of such systems, and of their organization. An approach to this problem is to consider the relationship between the behavioral functions of the prefrontal divisions and the characteristics of stimulation-induced reward obtained at each site. Studies of the effects of restricted prefrontal lesions indicate that the medial and sulcal divisions can be dissociated according to their involvement in the control of distinct types of sensory and motor events. Further experiments indicate that damage to each division causes selective deficits in the learning of stimulus-reinforcer and response-reinforcer relations, depending in part on the nature of the reinforcing event. Conditioning experiments further show that the rewarding effects produced by stimulation of these areas are preferentially associated to sensory events which correspond to the functional specialization of each division. These data are interpreted to suggest that different rewarding events and/or different attributes of rewarding stimuli are processed by distinct systems which are reflected by the organization of dissociable self-stimulation pathways.

Animals↗