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 379 records · Page 21Linked to original sources

PubMed2003

Involvement of GABAA receptors in the regulation of the prefrontal cortex on dopamine release in the rat dorsolateral striatum.

The characteristics of the prefrontal cortex regulation of dopamine release in the rat dorsolateral striatum were investigated in focusing on the corticostriatal pathway, using dual-probe microdialysis in combination with simple behavioral procedures. Intracortical perfusion of the GABA(A) receptor antagonist bicuculline (0.03 and 0.1 mM) increased the striatal dopamine release, whereas the GABA(A) receptor agonist muscimol (0.1 and 1 mM) reduced the release dose dependently. Co-perfusion of muscimol (0.01 mM), which did not by itself affect the dopamine release, completely prevented the glutamate (1 mM)-stimulated dopamine release and behavioral activities, including locomotion and rearing. Muscimol (0.01 mM) also prevented the N-methyl-D-aspartate (NMDA; 1 mM)-induced increases in glutamate, as well as dopamine levels. These findings suggest that the prefrontal cortex functionally regulates dopamine release in the dorsolateral striatum, which is mediated via GABA(A) receptors. This cortical GABAergic system underlying the prefrontal cortex regulatory mechanism appears to be associated with the corticostriatal pathway.

Animals↗

PubMed2003

Working memory and prefrontal cortex dysfunction: specificity to schizophrenia compared with major depression.

BACKGROUND: A large number of studies suggest the presence of deficits in dorsolateral prefrontal cortex function during performance of working memory tasks in individuals with schizophrenia. However, working memory deficits may also present in other psychiatric disorders, such as major depression. It is not clear whether people with major depression also demonstrate impaired prefrontal activation during performance of working memory tasks. METHODS: We used functional magnetic resonance imaging to assess the patterns of cortical activation associated with the performance of a 2-back version of the N-Back task (working memory) in 38 individuals with schizophrenia and 14 with major depression. RESULTS: We found significant group differences in the activation of dorsolateral prefrontal cortex associated with working memory performance. Consistent with prior research, participants with schizophrenia failed to show activation of right dorsolateral prefrontal cortex in response to working memory tasks demands, whereas those with major depression showed clear activation of right and left dorsolateral prefrontal cortex as well as bilateral activation of inferior and superior frontal cortex. CONCLUSIONS: During performance of working memory tasks, deficits in prefrontal activation, including dorsolateral regions, are more severe in participants with schizophrenia (most of whom were recently released outpatients) than in unmedicated outpatients with acute nonpsychotic major depression.

Adult↗

PubMed1997

Short- and long-term plasticity of the hippocampus to nucleus accumbens and prefrontal cortex pathways in the rat, in vivo.

The pathways from the hippocampal formation to the nucleus accumbens and the prefrontal cortex are likely to play a role in several aspects of learning and memory. In the present study we addressed the question of how plastic changes in these structures may occur simultaneously. This question can be studied in an appropriate way in the hippocampal/fornix-fimbria to prefrontal cortex/nucleus accumbens system, since electrical stimulation of the fornix-fimbria fibre bundle evokes characteristic field potentials in the two target areas simultaneously. First, we examined the termination field in the nucleus accumbens (medial shell and core region with an extension into the ventro-medial caudate-putamen) and the prefrontal cortex (deeper layers of the ventral prelimbic and ventral infralimbic areas) by recording single unit activity evoked by stimulation of fornix-fimbria fibres in halothane anaesthetized rats. Second, we studied short-term plasticity, namely paired pulse facilitation, in these two areas upon stimulation of the fornix-fimbria fibres. In the nucleus accumbens, paired pulse facilitation was encountered for double pulse intervals between 25 and 500 ms, peaking around 100 ms. In the medial prefrontal cortex it was confined to intervals between 25 and 200 ms, with a peak around 75 ms. Third, we investigated whether LTP could be elicited simultaneously in the two target structures by a single tetanic stimulation (50 Hz, 2 s) of the fornix-fimbria fibres. LTP that was sustained for more than 90 min in the medial prefrontal cortex, reached levels of 130% of control values. In the nucleus accumbens, however, only a transient form of potentiation was found which lasted no more than 60 min. These data show that synaptic weights can be changed in several target structures of the hippocampal formation, simultaneously, in a distributed way.

Animals↗

PubMed2003

Instructed delay activity in the human prefrontal cortex is modulated by monetary reward expectation.

Goal-directed actions are executed with greater efficiency when the goals of the actions are rewarded and so the reward expectation must influence systems concerned with action-planning and motor control. However, little is known about how this influence is achieved in primates. Here, we demonstrate in human subjects that manual performance is enhanced when the goals of the visually cued actions are monetary rewards. We also used event-related fMRI in the same subjects to localize neural activity related to action preparation and selection that was influenced by the reward. We found three areas with significant interaction between reward and preparation: the prestriate visual cortex, the premotor cortex and the lateral prefrontal cortex. The latter two areas appear to be frontal systems integrating the expectation of rewards with selection and preparation of actions.

Analysis of Variance↗

PubMed1996

Differential effects of prenatal exposure to cocaine and amphetamine on growth parameters and morphometry of the prefrontal cortex in the rat.

The purpose of this study was to investigate the differential effects of prenatal exposure to psychostimulants, e.g., cocaine or amphetamine, on basic growth parameters and morphometry of the medial prefrontal cortex of the rat. A group of pregnant Wistar rats was given 60 mg/kg body weight/day of cocaine hydrochloride and another group 10 mg/kg body weight/day of d-amphetamine sulfate, subcutaneously, from gestational days 8 to 22. Control groups of pregnant rats were pair-fed; litters were culled to eight pups (4 males and 4 females) weighed every other day until postnatal day 30 and every week until day 90. The body weight growth patterns modelled by a Gompertz curve were different in rats prenatally exposed to the two psychostimulants. Rats exposed to amphetamine had on average a slower growth than those exposed to cocaine, reaching an identical estimated adult weight. Allometric relationships between forebrain and body weight and cerebellum and body weight were described by two distinct postnatal growth phases that are different among the experimental groups. In the comparison of the two psychostimulants the relative cerebellum/body growth is lower in the offspring of the cocaine group than in the amphetamine group between PND14-PND30; between PND30-PND90 the relative growth rate is considerably higher in the offspring of the cocaine dams compared to that of the amphetamine dams. Groups of perfused animals were selected at postnatal days 14 and 30 to analyze the morphometric organization of the medial prefrontal cortex. In serial celloidin sections the volumes of the prefrontal cortex were determined; the number of neurons per unit volume of reference area was calculated using the stereological technique of the disector. The changes found in the morphometric parameters show a catch-up at postnatal day 30 of the "increased" density of neurons of the medial prefrontal cortex found at postnatal day 14. These data show differential growth patterns of offspring from cocaine- and amphetamine-exposed rats; a delayed development in the achievement of normal morphometric parameters of neurons in the prelimbic subarea of the medial prefrontal cortex occurs in the prenatally amphetamine-exposed offspring at early ages, and a catch-up is found after the first month of life. Complementary studies are needed to assess whether these changes have functional implications in the rats exposed prenatally to psychostimulants.

Amphetamine↗

PubMed1999

No change in the density of the serotonin1A receptor, the serotonin4 receptor or the serotonin transporter in the dorsolateral prefrontal cortex from subjects with schizophrenia.

Changes in serotonin receptors and the serotonin transporter have been reported in the dorsolateral prefrontal cortex from subjects with schizophrenia, an area of the brain thought to be important in the pathology of the illness. To further our understanding on how such changes could play a role in the pathology of the illness, in situ radioligand binding with autoradiography was used to measure the density of the serotonin1A receptor, the serotonin4 receptor and the serotonin transporter in the dorsolateral prefrontal cortex, obtained at autopsy, from 10 schizophrenic and 10 control subjects. The binding of [3H]8-OH-DPAT to serotonin1A receptor, [3H]GR113808 to the 5HT4 receptor and [3H]citalopram to serotonin transporter was not altered in subjects with schizophrenia. significantly, only in tissue from the control subjects was there a relationship between age and the density of the serotonin4 receptor in Brodmann's areas 8 (r = 0.71, P = 0.02) and 10 (r = -0.67, P = 0.03). Importantly, this confounding factor did not influence the comparison of the density of serotonin4 receptor in the tissue from the schizophrenic and control subjects. This study has failed to show a difference in the density of serotonin1A receptor, the serotonin4 receptor or the serotonin transporter in the dorsolateral prefrontal cortex (Brodmann's areas 8, 9 and 10) from subjects with schizophrenia. These data suggest that not all serotonergic markers are altered in the dorsolateral prefrontal cortex from schizophrenic subjects.

Carrier Proteins↗

PubMed1998

Involvement of gamma-aminobutyric acid neurotransmission in phencyclidine-induced dopamine release in the medial prefrontal cortex.

The present study was designed to examine the possible involvement of gamma-aminobutyric acid (GABA) neurotransmission in the mechanism of phencyclidine (1-(1-phenylcyclohexyl)piperidine; PCP)-induced dopamine release in the medial prefrontal cortex, using in vivo microdialysis in awake, freely moving rats. Local perfusion via the dialysis probe into the medial prefrontal cortex with PCP (100 and 500 microM) and dizocilpine ((+)-5-methyl-10,11-dihydroxy-5-H-dibenzo(a,d)cyclo-heptan-5,10-im ine; MK-801, 10 and 50 microM), a selective non-competitive NMDA receptor antagonist, was found to increase extracellular dopamine levels. Co-perfusion with NMDA (1 mM) or the GABAA receptor agonist muscimol (50 microM) attenuated the effects of PCP (500 microM) and MK-801 (50 microM) on extracellular dopamine levels. The dopamine reuptake inhibitor nomifensine (50 microM) also produced an increase in extracellular dopamine levels in the medial prefrontal cortex, but this effect was not affected by co-perfusion with muscimol (50 microM). On the other hand, local perfusion with PCP (100 and 500 microM) and MK-801 (10 and 50 microM), but not nomifensine (50 microM), reduced extracellular GABA levels in the medial prefrontal cortex. Co-perfusion with NMDA (1 mM) reduced the effects of PCP (500 microM) and MK-801 (50 microM) on extracellular GABA levels. These results suggest that PCP may facilitate dopamine release in the medial prefrontal cortex, at least in part, by the inhibition of GABA release via the antagonism of NMDA receptors.

Animals↗

PubMed2003

Reduced basal and phencyclidine-induced expression of heat shock protein-70 in rat prefrontal cortex by the atypical antipsychotic abaperidone.

The effect of antipsychotic treatment on basal and phencyclidine (PCP)-induced heat shock protein-70 (hsp70) mRNA expression was studied in the rat striatum and in the prefrontal cortex. Abaperidone, a novel drug with an atypical antipsychotic profile, was compared, at pharmacologically equivalent doses, with the atypical antipsychotics clozapine and risperidone and also with haloperidol, a classical antipsychotic. Abaperidone and clozapine reduced basal hsp70 mRNA expression in the rat striatum and in the prefrontal cortex. No change in either region was found after haloperidol, whereas risperidone reduced hsp70 mRNA in the striatum but not in the prefrontal cortex. The N-methyl-D-aspartate (NMDA) receptor antagonist PCP significantly elevated hsp70 mRNA levels in the prefrontal cortex, an elevation that was potentiated by haloperidol and prevented by all of the atypical antipsychotics tested. Since hsp70 has been associated to some schizophrenia symptoms, we suggest that reduced hsp70 in the prefrontal cortex, a cortical area that plays a critical role in the etiology of many schizophrenia symptoms, may be linked to an atypical profile of antipsychotics, such as clozapine, and possibly also abaperidone.

Animals↗

PubMed2000

Effect of amphetamine on extracellular acetylcholine and monoamine levels in subterritories of the rat medial prefrontal cortex.

The present study sought to investigate the contributions of the dorsal prelimbic/anterior cingulate and ventral prelimbic/infralimbic cortices to the reverse microdialysis of amphetamine (1, 10, 100, 500, and 1000 microM) on dialysate acetylcholine, choline, norepinephrine, and serotonin levels. The results demonstrate that basal levels of acetylcholine, choline, and serotonin were homogeneous within subregions of the medial prefrontal cortex. In contrast, dialysate norepinephrine levels were significantly higher in the anterior cingulate cortex compared with the infralimbic cortex. Reverse microdialysis of amphetamine in both subareas of the medial prefrontal cortex produced a dose-dependent increase in norepinephrine and serotonin levels; the magnitude of this effect was similar in both subterritories of the medial prefrontal cortex. Microinfusion of amphetamine increased dialysate acetylcholine levels in a dose-dependent manner only in the infralimbic cortex. Finally, amphetamine decreased choline levels in both subregions of the medial prefrontal cortex. The magnitude of this effect was larger in the anterior cingulate cortex compared with its infralimbic counterpart. Since depletions of frontal cortical acetylcholine result in severe cognitive deficits, the present data raise the possibility that the type of neural integrative processes that acetylcholine mediates depends, at least in part, on the subterritories that characterize the medial prefrontal cortex.

Acetylcholine↗

PubMed1997

Prefrontal cortex cognitive deficits in children treated early and continuously for PKU.

To begin to study the importance of dopamine for executive function abilities dependent on prefrontal cortex during early childhood, the present investigation studied children in whom we predicted reduced dopamine in prefrontal cortex but otherwise normal brains. These are children treated early and continuously for the metabolic disorder phenylketonuria (PKU). Untreated PKU is the most common biochemical cause of mental retardation. The root problem is an inability to convert one amino acid, phenylalanine (Phe), into another, tyrosine (Tyr), the precursor of dopamine. Phe levels in the bloodstream soar; Tyr levels fall. Treatment with a diet low in Phe reduces the Phe:Tyr imbalance but cannot eliminate it. We hypothesized that the resultant modest elevation in the ratio of Phe to Tyr in the blood, which results in slightly less Tyr reaching the brain, uniquely affects the cognitive functions dependent on prefrontal cortex because of the special sensitivity of prefrontally projecting dopamine neurons to small decreases in Tyr. In a 4-year longitudinal study, we found that PKU children whose plasma Phe levels were three to five times normal (6-10 mg/dl) performed worse than other PKU children with lower Phe levels, matched controls, their own siblings, and children from the general population on tasks that required the working memory and inhibitory control abilities dependent on dorsolateral prefrontal cortex. The impairment was as evident in our oldest age range (3 1/2-7 years) as it was in the youngest (6-12 months). The higher a child's Phe level, the worse that child's performance. Girls were more adversely affected than boys. The deficit appears to be selective, affecting principally one neural system, since even PKU children with Phe levels three to five times normal performed well on the 13 control tasks. Clinical implications for the treatment of PKU and other neurodevelopmental disorders are discussed.

Age Factors↗

PubMed2004

Relation between asymmetry of prefrontal cortex activities and the autonomic nervous system during a mental arithmetic task: near infrared spectroscopy study.

The present study evaluated the relationship between asymmetry of the prefrontal cortex activity and the automatic nervous system (ANS) response during a mental arithmetic (MA) task. Employing near infrared spectroscopy, we compared cerebral blood oxygenation changes in the right and left prefrontal cortices during a mental arithmetic task with HR changes. During the MA task, eight subjects (high-HR group) showed large HR increases (14.2 +/- 3.0) while eight subjects (low-HR group) showed small HR increases (3.6 +/- 2.8) (P < 0.00001). In both the high-HR and low-HR groups, near infrared spectroscopy (NIRS) demonstrated increases of oxyhemoglobin and total hemoglobin (=oxyhemoglobin + deoxyhemoglobin) associated with decreases of deoxyhemoglobin in the bilateral prefrontal cortices during MA task. In the high-HR group, the laterality ratio scores, i.e., [(R - L)/(R + L) of oxyhemoglobin and total hemoglobin], showed positive values (0.17 +/- 0.11 and 0.17 +/- 0.17, respectively), while in the low-HR group, the laterality ratio scores showed negative values (-0.28 +/- 0.21 and -0.35 +/- 0.24, respectively). In addition, there were significant positive correlations between HR changes and the laterality ratio scores of oxyhemoglobin (r = +0.87, P < 0.0001) and total hemoglobin (r = +0.85, P < 0.0001). These results indicate that the MA task-induced activity in the right prefrontal cortex was larger than that in the left prefrontal cortex in the subject with high HR increases, suggesting that the right prefrontal cortex activity during the MA task has a greater role in cerebral regulation of HR by virtue of decreasing parasympathetic effects or increasing sympathetic effects.

Adult↗

PubMed1986

Prefrontal cortex neuron activity during a discriminative conditioning paradigm in unanesthetized rats.

Single neuron responses were recorded from the prefrontal cortex of unanesthetized, restrained rats trained to a discriminative conditioning paradigm. The animals were preconditioned to a tone paired with footshock (CS+) and a second tone presented unpaired (CS-). Only neurons with large amplitude, positive first deflection action potentials were studied. Eighty-five percent of the units (17 of 20) emitted conditioned responses in that the response to either one or both of the conditioned stimuli (CS) was significantly different from spontaneous activity. Thirty-five percent of the units emitted differential conditioned responses in that the responses to one of the CS was significantly different than the response to the other CS and that the response was subsequently shown to extinguish when the footshock was withheld. The neurons which emitted the differential conditioned responses appeared to be located in the deeper layers of the anteromedial prefrontal cortex while the remaining neurons were located either in more superficial layers or anterior aspects of the prefrontal cortex. The results suggest that the anteromedial prefrontal cortex may be involved in neural mechanisms related to discriminative conditioning.

Action Potentials↗

PubMed1996

Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression.

BACKGROUND: Lesion and neuroimaging studies suggest that left prefrontal lobe dysfunction is pathophysiologically linked to depression. Rapid-rate transcranial magnetic stimulation (rTMS) to prefrontal structures has a lateralised effect on mood in normal volunteers, and several preliminary studies suggest a beneficial effect of rTMS on depression. However, adequately controlled studies have not been conducted. METHODS: We have studied the effects of focal rTMS on the depressive symptoms in 17 patients with medication-resistant depression of psychotic subtype. The study was designed as a multiple cross-over, randomised placebo-controlled trial. Sham rTMS and stimulation of different cortical areas were used as controls. FINDINGS: Left dorsolateral prefrontal cortex rTMS resulted in a significant decrease in scores on the Hamilton depression rating scale HDRS (from 25.2 to 13.8) and the self-rated Beck questionnaire BQ (from 47.9 to 25.7). 11 of the 17 patients showed pronounced improvement that lasted for about 2 weeks after 5 days of daily rTMS sessions. No patient experienced any significant undesirable side-effects. INTERPRETATION: Our findings emphasise the role of the left dorsolateral prefrontal cortex in depression, and suggest that rTMS of the left dorsolateral prefrontal cortex might become a safe, non-convulsive alternative to electroconvulsive treatment in depression.

Adult↗

PubMed1994

Deficient sensorimotor gating after 6-hydroxydopamine lesion of the rat medial prefrontal cortex is reversed by haloperidol.

The present study sought to test the hypothesis that dopamine in the prefrontal cortex exerts an inhibitory influence on subcortical dopamsine systems and that depletion of prefrontal dopamine may affect behaviour via an increase in dopamine release in the basal ganglia. We used prepulse inhibition of the acoustic startle response, i.e. the inhibition of the acoustic startle response by a preceding non-startling stimulus, as the behavioural test, because this phenomenon of sensorimotor gating is modified in opposite directions by dopamine in the prefrontal cortex and in the basal ganglia. Rats were tested for prepulse inhibition before and after injections of the neurotoxin 6-hydroxydopamine into the medial prefrontal cortex. We attempted to differentiate the contributions of prefrontal dopamine and noradrenaline by pretreating the animals with desipramine (6-OHDAMI rats) or bupropion (6-OHDABUP rats), selective inhibitors of noradrenaline and dopamine reuptake respectively. 6-Hydroxydopamine lesion reduced prefrontal dopamine by 90% and noradrenaline by 80% in 6-OHDADMI rats, while prefrontal dopamine was reduced by 54% and noradrenaline by 95% in 6-OHDABUP rats. The ability of an acoustic prepulse (75 dB, 10 kHz) to inhibit the response to a startle pulse (100 dB noise burst) was maintained in sham-lesioned rats and in 6-OHDABUP rats. However, there was a marked reduction of prepulse inhibition (by 26%) in the 6-OHDADMI rats. Systemic administration of the dopamine antagonist haloperidol (0.05 mg/kg), which did not affect prepulse inhibition in sham-lesioned and in 6-OHDABUP rats, antagonized the lesion-induced deficit in prepulse inhibition in 6-OHDADMI rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

PubMed1996

Behavioural effects of ablations of the presumed 'prefrontal cortex' or the corticoid in pigeons.

This study further explored functional similarities of mammalian prefrontal cortex and its presumed equivalent in pigeons. Our results show that the performance of delayed alternation of pigeons in an Y-maze is impaired following ablations of the prefrontal equivalent together with the corticoid but not of the corticoid alone. In the same maze, discrimination between vertical and horizontal stripes was unimpaired regardless of the lesion. Our results added the following new information. (1) Corticoid is not essentially involved in mediation of delayed responding. (2) Like monkeys, pigeons take much fewer trials to learn delayed alternation in a maze than in an operant chamber. (3) Lesions of the pigeon equivalent of the prefrontal cortex impair delayed responding also in the new apparatus. (4) These lesions do not impair visual pattern discrimination. Our results do not contradict the hypothesis that the postero-dorso-lateral neostriatum in pigeons is comparable to the prefrontal cortex in mammals.

Animals↗

PubMed1987

Circling behavior following unilateral microinjections of cocaine into the medial prefrontal cortex: dopaminergic or local anesthetic effect?

Dopaminergic projections to the medial prefrontal cortex have been implicated in cocaine reinforcement; therefore, it was of interest to examine the locomotor effects of acute administration of cocaine to this area. Circling behavior was assessed following injections of 1.0 microliter of cocaine in doses of 0 (0.9% saline), 25, 50, and 100 micrograms/microliters into the medial prefrontal cortex of rats prepared with chronic unilateral guide cannulae. Animals were scored during four 5 min intervals of a 60 min test session that began with the central injection and placement in a flat circular arena. Cocaine was found to produce dose-dependent contraversive circling, an effect previously seen with the dopamine (DA) agonists LY 14 1865 and (+)-amphetamine, suggesting a unilateral stimulant effect. However, since cocaine has potent local anesthetic properties that have been reported to produce behavioral effects and also to inhibit the reuptake of norepinephrine and 5-HT, it was important to demonstrate that the directional bias was a dopaminergic effect. Intra-frontocortical microinjections of the local anesthetic procaine (10, 100, and 1000 micrograms in 0.5 microliter) did not induce circling. Sulpiride (0.001-10.0 micrograms in 0.5 microliter), a DA antagonist specific for the D-2 receptors, produced ipsiversive circling in a dose-dependent manner in rats treated with (+)-amphetamine (1.5 mg/kg, i.p.). In addition, sulpiride (1.0 micrograms in 0.5 microliter) blocked the circling behavior induced by cocaine (50 micrograms in 0.5 microliter) when administered into the medial prefrontal cortex 15 min prior to the cocaine injection. These results provide further evidence for an excitatory influence of mesocortical DA on motor control.

Anesthesia, Local↗

PubMed1987

Reduced haloperidol and haloperidol: effects on homovanillic acid in caudate and prefrontal cortex.

The effects of acute administration of reduced haloperidol (RHAL) on homovanillic acid (HVA) in the caudate and prefrontal cortex were examined in rats. Haloperidol (HAL) was used as a reference compound. Concentrations of HVA and HAL were measured by HPLC/ECD. The maximal HVA response time was 3 hr after the injection, in both caudate and prefrontal cortex, for both RHAL and HAL. The potency of RHAL in the elevations of HVA in the caudate and prefrontal cortex was only about one-third to one-fifth that of HAL. The concentrations of HAL in the prefrontal cortex and caudate after RHAL administration were just about one-third to one-fifth those after HAL administration. These results suggest that less antidopaminergic activity of RHAL in this neuroleptic test might be explained by the lesser conversion of RHAL to HAL.

Animals↗

PubMed2004

Stimulus-specific plasticity of prefrontal cortex dopamine neurotransmission.

Future planning and behavioral modification is thought to require experience-dependent plasticity in neuronal circuits involving the prefrontal cortex, nucleus accumbens and amygdala. Dopamine has been implicated in such plasticity; however, the nature of the adaptive response of dopamine systems to emotionally salient experiences is poorly understood. We determined whether the dopaminergic response to a given stimulus changes after the first exposure to that stimulus and whether this alteration is stimulus specific. Dopamine release was measured in the prefrontal cortex and the nucleus accumbens in response to two aversive but qualitatively distinct stimuli, physical restraint and electrical microstimulation of basolateral amygdala. In the prefrontal cortex, the first exposure to restraint or amygdala stimulation produced similar increases in dopamine release. The second exposure to restraint resulted in an attenuated response (- 36%) whereas the second exposure to amygdala stimulation produced a potentiated response (+ 110%). Cross-modal potentiation of response occurred with both stimuli. These adaptive changes were specific to the prefrontal cortex and were not observed in the nucleus accumbens. These findings demonstrate that prefrontal cortical dopamine output adapts after a single exposure to stimuli with emotional salience. The direction of this adaptation, however, is not uniform and depends on the nature of the stimulus.

Amygdala↗