SEARCH · PubMed Health

Results for “Prefrontal Cortex”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

PubMed2000

Dopamine terminals synapse on callosal projection neurons in the rat prefrontal cortex.

Dopamine (DA) afferents to the prefrontal cortex (PFC) play an important role in the cognitive functions subserved by this cortical area. Within the PFC, DA terminals synapse onto the distal dendrites of both local circuit neurons and pyramidal projection cells. We have previously demonstrated in the rat PFC that some of the dendrites and spines postsynaptic to DA terminals arise from pyramidal neurons that project to the nucleus accumbens. However, it is not known whether the pyramidal cells that give rise to callosal intercortical connections of the PFC also receive DA synaptic input. To address this question, retrograde tract tracing using an attenuated strain of pseudorabies virus (PRV-Bartha) was combined with immunocytochemistry for tyrosine hydroxylase (TH) to identify DA terminals in the PFC. Thirty-six to 40 hours following injection of PRV into the contralateral PFC, numerous callosal projection neurons were extensively labeled throughout their dendritic trees, with no evidence of PRV trans-synaptic passage. In tissue prepared for electron microscopy, labeling for PRV was distributed throughout pyramidal cell somata and extended into distal dendrites and dendritic spines. Some PRV-labeled dendrites and spines received symmetric synaptic input from terminals containing peroxidase labeling for TH. These results demonstrate that DA terminals synapse onto the distal dendrites of callosally projecting PFC neurons and suggest substrates through which DA may modulate interhemispheric cortical communication.

Animals↗

PubMed2003

Spatiotemporal characteristics of hemodynamic changes in the human lateral prefrontal cortex during working memory tasks.

The prefrontal cortex (PFC) is widely believed to subserve mental manipulation and monitoring processes ascribed to the central executive (CE) of working memory (WM). We attempted to examine and localize the CE by functional imaging of the frontal cortex during tasks designed to require the CE. Using near-infrared spectroscopy, we studied the spatiotemporal dynamics of oxygenated hemoglobin (oxy-Hb), an indicator of changes in regional cerebral blood flow, in both sides of lateral PFC during WM intensive tasks. In most participants, increases in oxy-Hb were localized within one subdivison during performance of the n-back task, whereas oxy-Hb increased more diffusely during the random number generation (RNG) task. Activation of the ventrolateral PFC (VLPFC) was prominent in the n-back task; both sustained and transient dynamics were observed. Transient dynamics means that oxy-Hb first increases but then decreases to less than 50% of the peak value or below the baseline level before the end of the task. For the RNG task sustained activity was also observed in the dorsolateral PFC (DLPFC), especially in the right hemisphere. However, details of patterns of activation varied across participants: subdivisions commonly activated during performance of the two tasks were the bilateral VLPFCs, either side of the VLPFC, and either side of the DLPFC in 4, 2, and 4 of the 12 participants, respectively. The remaining 2 of the 12 participants had no regions commonly activated by these tasks. These results suggest that although the PFC is implicated in the CE, there is no stereotyped anatomical PFC substrate for the CE.

Adult↗

PubMed2004

Dominance attributions following damage to the ventromedial prefrontal cortex.

Damage to the human ventromedial prefrontal cortex (VM) can result in dramatic and maladaptive changes in social behavior despite preservation of most other cognitive abilities. One important aspect of social cognition is the ability to detect social dominance, a process of attributing from particular social signals another person's relative standing in the social world. To test the role of the VM in making attributions of social dominance, we designed two experiments: one requiring dominance judgments from static pictures of faces, the second requiring dominance judgments from film clips. We tested three demographically matched groups of subjects: subjects with focal lesions in the VM (n = 15), brain-damaged comparison subjects with lesions excluding the VM (n = 11), and a reference group of normal individuals with no history of neurological disease (n = 32). Contrary to our expectation, we found that subjects with VM lesions gave dominance judgments on both tasks that did not differ significantly from those given by the other groups. Despite their grossly normal performance, however, subjects with VM lesions showed more subtle impairments specifically when judging static faces: They were less discriminative in their dominance judgments, and did not appear to make normal use of gender and age of the faces in forming their judgments. The findings suggest that, in the laboratory tasks we used, damage to the VM does not necessarily impair judgments of social dominance, although it appears to result in alterations in strategy that might translate into behavioral impairments in real life.

Brain Damage, Chronic↗

PubMed2002

Neonatal prefrontal cortex lesion using CO2 laser technique.

Prefrontal cortex (PFC) is a large area of the brain and its neonatal lesion with ibotenic or kainic acid is used to study the early abnormalities in neurodevelopment that lead to behavioral changes linked to schizophrenia. However, these exitotoxic drugs produce a large and asymmetric damage in the PFC. We produced the bilateral lesions of the dorsal part of the PFC of neonatal Sprague-Dawley rats (postnatal day 7, P7) at the anteroposterior +2.5 mm and mediolateral +/-0.4 coordinates by the new laser technique that employ the confined radiation of the CO(2) laser in the pulsed mode. The laser was used because its coherent radiation can be focused in a very small spot and as small as of several tens of micrometers in diameters. The CO(2) laser radiation is strongly absorbed by water that is present in any soft tissue. Thereafter, the configuration of the heated zone and, consequently, that of the lesion does not depend on the morphological non-homogeneity of particular structures. We obtained the symmetric, conical in shape and small-size bilateral lesions of the PFC. The size of the lesion depended on the beam spot-size and could be as small as several dozens of micrometers in diameter. Our data suggests that the laser technique will be used for the anatomical-functional studies of the PFC in the brain.

Animals↗

PubMed2004

Effects of neonatal lesions of the medial prefrontal cortex on adult rat behaviour.

While prefrontal lesions in rodents serve as models for frontal lobe syndromes, neonatal lesions are considered as models for disconnection syndromes, such as schizophrenia. We investigated the effect of neonatal lesions of the rat medial prefrontal cortex (mPFC) together with pubertal dexamethasone-challenge on adult rat behaviour and on apomorphine-induced behavioural changes. Adult lesions were used as controls. Rats with neonatal (postnatal day 7) or adult excitotoxic lesions or sham-lesions of the mPFC were tested 9 weeks after surgery. At postnatal day 49 one group of neonatal operated rats were systemically injected with the glucocorticoid receptor agonist dexamethasone (20 mg/kg), in order to simulate stress-induced glucocorticoid receptor activation. Working memory and perseveration was tested in T-maze tasks (continuous delayed alternation and reversal learning). Additionally, locomotor activity and prepulse inhibition (PPI) of startle was tested with and without apomorphine-treatment. Brain tissue damage was assessed using Nissl-staining and parvalbumine-immunocytochemistry. Pronounced thinning of the prelimbic-infralimbic subregion of the mPFC accompanied by altered cytoarchitecture and reduced number of parvalbumine-immunopositive neurones was found after neonatal lesions while adult lesions resulted in loss of neurones accompanied by gliosis. Neonatal lesions increased perseveration in the T-maze tasks and enhanced PPI, while adult lesions induced a working memory deficit. This differential behavioural outcome presumably reflects neurodevelopmentally induced alterations in neuronal circuits after neonatal lesions versus damage to mPFC alone after adult lesions. Dexamethasone-injection at day 49 did not alter behaviour in these tasks. Motor activity was not affected by neonatal or adult lesions but dexamethasone reduced apomorphine-induced hyperlocomotion.

Analysis of Variance↗

PubMed2004

Pressor effects of electrical stimulation of medial prefrontal cortex in unanesthetized rats.

The medial prefrontal cortex (MPFC) is involved in central nervous system (CNS)-mediated cardiovascular modulation. We compared the cardiovascular effects of electrical stimulation (EE) of the MPFC in unanesthetized rats to those observed after stimulation of the same area in urethane-anesthetized rats. Electrical stimulation (35, 106, 177, 247, 318, and 389 microA rms/10 sec, 60-Hz sine wave) of the MPFC of urethane-anesthetized rats caused depressor responses of stimulus-related intensity. The cardiovascular response to electrical stimulation of the MPFC in unanesthetized rats was characterized by stimulus-related pressor responses. No significant heart rate changes were observed during the EE period in any case. The pressor response to electrical stimulation (106 microA rms/10 sec, 60-Hz sine wave) of the MPFC was not affected by intravenous pretreatment with the vasopressin antagonist dTyr(CH(2))(5)(Me)AVP (50 microg/kg, intravenously), by hypophysectomy, or by intravenous pretreatment with the angiotensin II antagonist losartan (1 mg/kg, intravenously). The pressor response was blocked by intravenous pretreatment with the ganglionic blocker mecamylamine (2 mg/kg, intravenously) but was not affected by adrenal demedullation, thus suggesting involvement of the neural component of the sympathetic nervous system without a major involvement of its hormonal component. Our results confirmed the occurrence of depressor responses after electrical stimulation of the MPFC in urethane-anesthetized rats and evidenced that only pressor responses are observed after its stimulation in unanesthetized rats. The fact that the pressor response to the stimulation of the MPFC was blocked by a ganglioplegic suggests that the MPFC has functional excitatory actions over the sympathetic nervous system.

Adrenal Medulla↗

PubMed2005

Dopaminergic modulation of short-term synaptic plasticity in fast-spiking interneurons of primate dorsolateral prefrontal cortex.

Dopaminergic regulation of primate dorsolateral prefrontal cortex (PFC) activity is essential for cognitive functions such as working memory. However, the cellular mechanisms of dopamine neuromodulation in PFC are not well understood. We have studied the effects of dopamine receptor activation during persistent stimulation of excitatory inputs onto fast-spiking GABAergic interneurons in monkey PFC. Stimulation at 20 Hz induced short-term excitatory postsynaptic potential (EPSP) depression. The D1 receptor agonist SKF81297 (5 microM) significantly reduced the amplitude of the first EPSP but not of subsequent responses in EPSP trains, which still displayed significant depression. Dopamine (DA; 10 microM) effects were similar to those of SKF81297 and were abolished by the D1 antagonist SCH23390 (5 microM), indicating a D1 receptor-mediated effect. DA did not alter miniature excitatory postsynaptic currents, suggesting that its effects were activity dependent and presynaptic action potential dependent. In contrast to previous findings in pyramidal neurons, in fast-spiking cells, contribution of N-methyl-D-aspartate receptors to EPSPs at subthreshold potentials was not significant and fast-spiking cell depolarization decreased EPSP duration. In addition, DA had no significant effects on temporal summation. The selective decrease in the amplitude of the first EPSP in trains delivered every 10 s suggests that in fast-spiking neurons, DA reduces the amplitude of EPSPs evoked at low frequency but not of EPSPs evoked by repetitive stimulation. DA may therefore improve detection of EPSP bursts above background synaptic activity. EPSP bursts displaying short-term depression may transmit spike-timing-dependent temporal codes contained in presynaptic spike trains. Thus DA neuromodulation may increase the signal-to-noise ratio at fast-spiking cell inputs.

2-Amino-5-phosphonovalerate↗

PubMed1990

Acute effects of typical and atypical antipsychotic drugs on the release of dopamine from prefrontal cortex, nucleus accumbens, and striatum of the rat: an in vivo microdialysis study.

In vivo microdialysis has been used to study the acute effects of antipsychotic drugs on the extracellular level of dopamine from the nucleus accumbens, striatum, and prefrontal cortex of the rat. (-)-Sulpiride (20, 50, and 100 mg/kg i.v.) and haloperidol (0.1 and 0.5 mg/kg i.v.) enhanced the outflow of dopamine in the striatum and nucleus accumbens. In the medial prefrontal cortex, (-)-sulpiride at all doses tested did not significantly affect the extracellular level of dopamine. The effect of haloperidol was also attenuated in the medial prefrontal cortex; 0.1 mg/kg did not increase the outflow of dopamine and the effect of 0.5 mg/kg haloperidol was of shorter duration in the prefrontal cortex than that observed in striatum and nucleus accumbens. The atypical antipsychotic drug clozapine (5 and 10 mg/kg) increased the extracellular concentration of dopamine in all three regions. In contrast to the effects of sulpiride and haloperidol, that of clozapine in the medial prefrontal cortex was profound. These data suggest that different classes of antipsychotic drugs may have distinct effects on the release of dopamine from the nigrostriatal, mesolimbic, and mesocortical terminals.

Animals↗

PubMed1997

BIMG 80, a novel potential antipsychotic drug: evidence for multireceptor actions and preferential release of dopamine in prefrontal cortex.

In radioligand binding studies, BIMG 80, a new putative antipsychotic, displayed good affinity at certain serotonin (5-HT1A, 5-HT2A, 5-HT6), dopamine (D1, D2L, D4), and noradrenergic (alpha1) receptors. The effect of acute subcutaneous BIMG 80, clozapine, haloperidol, risperidone, amperozide, olanzapine, and Seroquel was then investigated on dopamine release in medial prefrontal cortex, nucleus accumbens, and striatum in freely moving rats using the microdialysis technique. Four different neurochemical profiles resulted from the studies: (a) Systemic administration of BIMG 80, clozapine, and amperozide produced greater percent increases in dopamine efflux in medial prefrontal cortex than in the striatum or the nucleus accumbens. (b) Haloperidol induced a similar increase in dopamine concentrations in the striatum and nucleus accumbens with no effect in the medial prefrontal cortex. (c) Risperidone and olanzapine stimulated dopamine release to a similar extent in all brain regions investigated. (d) Seroquel failed to change significantly dopamine output both in the medial prefrontal cortex and in the striatum. Because an increase in dopamine release in the medial prefrontal cortex may be predictive of effectiveness in treating negative symptoms and in the striatum may be predictive of induction of extrapyramidal side effects, BIMG 80 appears to be a potential antipsychotic compound active on negative symptoms of schizophrenia with a low incidence of extrapyramidal side effects.

Animals↗

PubMed1989

Prefrontal cortex gating of auditory transmission in humans.

Middle-latency auditory evoked potentials (MAEPs) were recorded in controls and patients with focal lesions in dorsolateral prefrontal cortex. Unilateral prefrontal lesions increased the amplitude of the Pa component of the MAEP beginning at 25-35 ms poststimulus. The data suggest that prefrontal cortex exerts early inhibitory modulation of input to primary auditory cortex in humans.

Acoustic Stimulation↗

PubMed2002

Alterations in time-place learning induced by lesions to the rat medial prefrontal cortex.

This experiment examined the effect of medial prefrontal lesions on time-place learning in the rat. During the first phase, prior to lesioning, rats received training on an interval time-place task. Food was available on each of four levers for 3 consecutive min of a 12-min session. The levers provided food in the same sequence on all trials. Rats restricted the majority of their presses on each lever to the time in each session when it provided food and were able to anticipate when a lever was going to provide food. During the second phase some rats received lesions that were restricted to the medial prefrontal cortex. Following these very restricted lesions, rats continued pressing a lever after it stopped providing food (i.e. perseverated, as if their internal clock was running slow). The third phase involved changing the order in which the levers provided food. Lesions had no discernable effect on the rats' ability to learn the correct sequence of food availability. However, this change made the rats' timing perseveration even more noticeable. Our results suggest the medial prefrontal cortex is not necessary for acquisition of time-place sequencing information. However, lesions do appear to produce perseveration on components of the sequence.

Journal Article↗

PubMed2003

The CB1 receptor antagonist SR141716A selectively increases monoaminergic neurotransmission in the medial prefrontal cortex: implications for therapeutic actions.

1. In order to explore potential therapeutic implications of cannabinoid antagonists, the effects of the prototypical cannabinoid antagonist SR141716A on monoamine efflux from the medial prefrontal cortex and the nucleus accumbens of the rat were investigated by in vivo microdialysis. 2. SR141716A moderately increased serotonin efflux and concentrations of its metabolite 5-HIAA, both in the medial prefrontal cortex and the nucleus accumbens, and increased norepinephrine, dopamine and their metabolites in the medial prefrontal cortex. In contrast, it had no effect on norepinephrine, dopamine and their metabolites in the nucleus accumbens. 3. At the same doses, SR141716A increased acetylcholine efflux in the medial prefrontal cortex, in agreement with previous studies; contrary to the effects in cortex, SR141716A had no effect on acetylcholine efflux in the nucleus accumbens. 4. The efficacy of SR141716A in the psychostimulant-induced hyperlocomotion and the forced swimming paradigms was also explored in mice. SR141716A attenuated phenylcyclidine- and d-amphetamine-induced hyperlocomotion, without affecting locomotor activity when administered alone, and decreased immobility in the forced swimming test. 5. These results suggest that the cortical selectivity in the release of catecholamines, dopamine in particular, induced by the cannabinoid antagonist SR141716A, its procholinergic properties, together with its mild stimulatory effects on serotonin and norepinephrine efflux make similar compounds unique candidates for the treatment of psychosis, affective and cognitive disorders.

Animals↗

PubMed1991

[Effects of electrical or chemical stimulation of the prefrontal cortex on arrhythmias induced in cats by electrical stimulation of the anteromedial hypothalamus].

When the anteromedial hypothalamus is stimulated with a chronically implanted electrode in conscious cats, negative emotional behaviors such as restlessness and escape occur during stimulation and ventricular extrasystoles occur in rapid succession immediately after the end of stimulation. It has been shown in the lightly anesthetized cat that the activity of the sympathetic nervous system becomes predominant during stimulation of the anteromedial hypothalamus thereby causing the rises in blood pressure and heart rate. However, immediately after the cessation of the stimulation, this 'sympathetic dominant' state was observed to be switched to the 'parasympathetic dominant' state with falls in blood pressure and heart rate which was very frequently followed by the appearance of the ventricular extrasystoles (Poststimulus Arrhythmia: PSA). The purpose of this experiment was to examine how the electric and pharmacological stimulation of the prefrontal cortex modulate the rise in the blood pressure and heart rate and PSA caused by electric stimulation of the anteromedial hypothalamus. When the prefrontal cortex was electrically stimulated simultaneously with stimulation of the anteromedial hypothalamus in 24 lightly anesthetized cats, PSA was inhibited or facilitated or remained unchanged depending on the site of stimulation in the prefrontal cortex. When dopamine or noradrenaline was microinjected into the site of prefrontal cortex where PSA was inhibited, PSA was suppressed and this effect was blocked by microinjection of haloperidol or phenoxybenzamine, respectively. Dopamine was ineffective when injected in the site where PSA was facilitated; PSA was facilitated by microinjection of noradrenaline and this effect was inhibited by microinjection of propranolol. Although changes in blood pressure and heart rate were observed when the inhibition or facilitation of PSA was elicited by prefrontal injection of noradrenaline, no changes in cardiovascular parameters occurred when dopamine injection caused the inhibition of PSA. These results suggest (1) that activation of the dopamine receptor or alpha adrenoceptor in the prefrontal cortex is involved in the inhibition of PSA, and activation of beta adrenoceptor is concerned with facilitation of PSA and (2) that the mechanisms of dopamine receptor mediated inhibition of PSA appear to be different from those of inhibition of PSA by activation of the alpha adrenoceptor in the prefrontal cortex.

Animals↗

PubMed1994

Stress-induced sensitization of dopamine and norepinephrine efflux in medial prefrontal cortex of the rat.

We examined whether prior exposure to chronic cold (17-28 days, 5 degrees C) alters basal or stress-evoked (30-min tail shock) catecholamine release in medial prefrontal cortex, nucleus accumbens, and striatum, using in vivo microdialysis. Basal norepinephrine (NE) concentrations in medial prefrontal cortex did not differ between chronically cold-exposed rats and naive control rats (2.7 +/- 0.3 vs. 2.5 +/- 0.2 pg/20 microliters respectively). Basal dopamine (DA) efflux in any of the brain regions was not significantly different between chronically cold-exposed rats and naive rats. However, a trend for lower basal DA efflux in the cold-exposed relative to naive rats was observed in medial prefrontal cortex (1.5 +/- 0.2 vs. 2.2 +/- 0.3 pg/20 microliters, respectively), nucleus accumbens (3.7 +/- 0.8 vs. 5.4 +/- 0.9 pg/20 microliters, respectively), and striatum (4.4 +/- 0.5 vs. 7.2 +/- 1.5 pg/20 microliters, respectively). In medial prefrontal cortex of rats previously exposed to cold, tail shock elicited a greater increase from baseline in both DA and NE efflux relative to that measured in naive rats (DA, 2.3 +/- 0.3 vs. 1.2 +/- 0.1 pg, respectively; NE, 3.8 +/- 0.4 vs. 1.4 +/- 0.2 pg, respectively). However, in nucleus accumbens or striatum of rats previously exposed to cold, the stress-induced increase in DA efflux was not significantly different from that of naive rats (nucleus accumbens, 1.8 +/- 0.7 vs. 1.5 +/- 0.3 pg, respectively; striatum, 1.9 +/- 0.4 vs. 2.6 +/- 0.7 pg, respectively). Thus, both cortical NE projections and cortically projecting DA neurons sensitize after chronic exposure to cold. In contrast, subcortical DA projections do not sensitize under these conditions.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2006

Prefrontal cortex hemispheric specialization for categorical and coordinate visual spatial memory.

During visual spatial perception of multiple items, the left hemisphere has been shown to preferentially process categorical spatial relationships while the right hemisphere has been shown to preferentially process coordinate spatial relationships. We hypothesized that this hemispheric processing distinction would be reflected in the prefrontal cortex during categorical and coordinate visual spatial memory, and tested this hypothesis using functional magnetic resonance imaging (fMRI). During encoding, abstract shapes were presented in the left or right hemifield in addition to a dot at a variable distance from the shape (with some dots on the shape); participants were instructed to remember the position of each dot relative to the shape. During categorical memory retrieval, each shape was presented centrally and participants responded whether the previously corresponding dot was 'on' or 'off' of the shape. During coordinate memory retrieval, each shape was presented centrally and participants responded whether the previously corresponding dot was 'near' or 'far' from the shape (relative to a reference distance). Consistent with our hypothesis, a region in the left prefrontal cortex (BA10) was preferentially associated with categorical visual spatial memory and a region in the right prefrontal cortex (BA9/10) was preferentially associated with coordinate visual spatial memory. These results have direct implications for interpreting previous findings that the left prefrontal cortex is associated with source memory, as this cognitive process is categorical in nature, and the right prefrontal cortex is associated with item memory, as this process depends on the precise spatial relations among item features or components.

Adult↗

PubMed2001

Ventromedial prefrontal cortex lesions in humans eliminate implicit gender stereotyping.

Patients with prefrontal cortex lesions and controls were administered an implicit association task (IAT) that measured the degree of association between male and female names and their stereotypical attributes of strength and weakness. They also completed three questionnaires measuring their explicit judgment regarding gender-related stereotypical attributes. There were no between-group differences on the explicit measures. On the IAT, patients with dorsolateral lesions and controls showed a strong association, whereas patients with ventromedial prefrontal cortex lesions had a significantly lower association, between the stereotypical attributes of men and women and their concepts of gender. This finding provides support for the hypothesis that patients with ventromedial prefrontal lesions have a deficit in automatically accessing certain aspects of overlearned associated social knowledge.

Analysis of Variance↗

PubMed1990

Cocaine facilitates prefrontal cortex self-stimulation.

It has been demonstrated that cocaine HCl lowers thresholds for and increases rates of medial forebrain bundle intracranial self-stimulation. The influence of cocaine on prefrontal cortex self-stimulation was assessed in the present experiment. The prefrontal cortex was chosen because evidence indicates that the neuroanatomical and pharmacological substrate for intracranial self-stimulation at this site may differ from the substrate for medial forebrain bundle self-stimulation. Cocaine significantly decreased train-duration thresholds and increased the rate of prefrontal cortex self-stimulation. It was concluded that cocaine facilitates both prefrontal cortex and medial forebrain bundle self-stimulation, perhaps by influencing neural activity in the mesocorticolimbic dopamine system. However, the role of dopamine in cocaine's effects at both sites remains speculative.

Animals↗

PubMed1997

Contrasting effects of excitotoxic lesions of the prefrontal cortex on the behavioural response to D-amphetamine and presynaptic and postsynaptic measures of striatal dopamine function in monkeys.

The effects of excitotoxic lesions of the prefrontal cortex on behavioural, neurochemical and molecular indices of dopamine function in the caudate nucleus were studied in the marmoset. The lesion, which encompassed both the lateral and orbital regions of prefrontal cortex, made the animals more sensitive to the performance disrupting effects of the dopamine releasing drug, D-amphetamine, in a variation of the object retrieval task. Specifically, following drug administration, the lesioned marmosets were less able to gain access to food reward in the minimum number of responses. Analysis of the nature of the errors suggested that the deficit was not due to inhibition of a prepotent response as the lesioned monkeys were just as likely to make a detour reach to the unopened side of the box as a direct "line-of-sight" reach into the unopened front of the box. Rather, the data indicated a general disorganization of behaviour. The enhanced behavioural responsiveness to manipulations increasing presynaptic dopamine function was accompanied by neurochemical changes indicating a reduced responsiveness, as revealed by in vivo microdialysis. Thus, in lesioned animals, whilst there were no effects on baseline levels of extracellular dopamine in dorsolateral caudate, evoked release, both to systemic D-amphetamine and to a local depolarizing pulse of potassium ions, was attenuated. These opposite effects of the prefrontal cortex lesion on behavioural and neurochemical indices of striatal dopamine function occurred in the absence of any changes in striatal dopamine receptors of the D1 and D2 subtype, as determined both by radioligand binding assays and measurements of messenger RNA using in situ hydridization techniques. These data provide further insight into the interactions between prefrontal cortex and striatal dopamine function in the non-human primate. In particular, when taken in the light of our previous studies they indicate that following prefrontal manipulations, concurrence between behavioural and neurochemical indices of striatal dopamine function depends, critically, on the behavioural task. These findings are discussed with respect to the growing body of evidence implicating abnormalities in frontostriatal neurotransmission in complex disorders such as schizophrenia.

Analysis of Variance↗