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PubMed2003

Emotional valence modulates activity in the posterior fusiform gyrus and inferior medial prefrontal cortex in social perception.

Previous studies have shown that during the presentation of emotionally loaded visual stimuli, activity increases in the visual and limbic cortices. This study focuses on empathic reactions induced by presenting pictures of situations and facial expressions from a "third party" point of view only. We measured regional changes in blood flow (rCBF) in nine healthy subjects while they were looking at neutral, positive, or negative emotional pictures of low (facial expressions) and high (persons in real-life situations) social complexity. A significant rCBF increase occurred in the right posterior fusiform gyrus during presentation of emotional pictures of both low and high social complexity. We also observed an interaction between emotionality and social complexity in the left inferior occipital gyrus for situations, where emotionality produced a significantly larger rCBF increase for situations than faces. No significant rCBF changes were observed in the amygdala or other parts of the limbic system. A significant rCBF decrease was found in the right inferior medial prefrontal cortex during presentation of the emotional pictures. This is discussed with respect to the "default mode of the brain" theory. We suggest that there is a neural network in the posterior fusiform and inferior occipital gyrus specialized in identifying emotionally important visual clues. Messages from this and other areas converge to the medial prefrontal cortex, to be evaluated in terms of relevance for attention. We believe that this is a crucial part of a network used in normal empathic reactions and social interactions.

Adult↗

PubMed1989

[Effects of the stimulation of D1 and D2 dopaminergic receptors on the electrically induced release of gamma-(3H)-aminobutyric acid in the prefrontal cortex of the rat].

The effects of D1 and D2 dopaminergic agonists and antagonists on the electrically-evoked release of gamma-[3H] aminobutyric acid (3H-GABA) have been studied on rat prefrontal cortex slices. The major part of the electrically-evoked release of 3H-GABA appeared to be Ca++ dependent since a 62% decrease was observed when calcium was removed from the superfusion medium. Two specific D2 dopaminergic agonists, RU 24926 (10(-7) M) and lisuride (10(-6) M), respectively induced a 32% and a 50% inhibition of the electrically-evoked release of 3H-GABA. The selective D2 dopaminergic antagonists sulpiride (10(-5) M) totally abolished the effect of RU 24926 and partially abolished the effect of lisuride. The selective D1 agonist SKF 38393 (10(-5) M) did not affect 3H-GABA release. These results suggest that in the rat prefrontal cortex in vitro, the dopaminergic modulation of 3H-GABA release is mediated through D2 but not D1 receptors. The activation of D2 dopaminergic receptors induces an inhibition of the electrically-evoked release of 3H-GABA.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed2002

mRNA and protein expression of selective alpha subunits of G proteins are abnormal in prefrontal cortex of suicide victims.

The present investigation was undertaken to examine whether there is an abnormality in the expression of alpha and beta gamma subunits of G proteins both at the transcriptional and translational level in postmortem brain of adult and teenage suicide subjects and whether these abnormalities are related to mental disorders or suicide per se. In addition, an attempt has been made to investigate whether these abnormalities are similar or dissimilar in teenage and adult suicide, because the etiology of teenage suicide may be different than that of adults.A significant decrease in both mRNA and protein levels of G(i2)alpha and G(O)alpha and a significant increase in levels of G(s)alpha(-S) were observed in prefrontal cortex of suicide subjects (n = 43) compared with non-psychiatric control subjects (n = 38). When subjects were grouped according to age, a significantly decreased expression of G(i2)alpha and G(O)alpha and significantly increased expression of G(s)alpha(-S) were observed in adult suicide subjects (age > or = 20 yrs; n = 20) as compared with age-matched controls (n = 27). These changes were present in all adult suicide subjects regardless of psychiatric diagnosis. On the other hand, although there were no significant differences in any alpha or beta gamma subunits in teenage suicide subjects (age < or = 19 yrs; n = 16) when compared with matched control subjects (n = 18); however, mRNA and protein levels of G(i2)alpha and G(O)alpha were significantly decreased and of G(s)alpha(-S) were significantly increased only in those teenage suicide subjects who had a history of mental illness (n = 11). Our results suggest that there are defects in the expression of selective G protein alpha subunits in prefrontal cortex of adult and teenage suicide subjects, which appear to be related to mental disorders.

Adolescent↗

PubMed2004

Ventromedial prefrontal cortex and amygdala dysfunction during an anger induction positron emission tomography study in patients with major depressive disorder with anger attacks.

CONTEXT: Although a variety of functional neuroimaging studies have used emotion induction paradigms to investigate the neural basis of anger in control subjects, no functional neuroimaging studies using anger induction have been conducted in patient populations. OBJECTIVE: To study the neural basis of anger in unmedicated patients with major depressive disorder with anger attacks (MDD + A), unmedicated patients with MDD without anger attacks (MDD - A), and controls. DESIGN: We used positron emission tomography, psychophysiologic measures, and autobiographical narrative scripts in the context of an anger induction paradigm. SETTING: Academic medical center. PARTICIPANTS: Thirty individuals, evenly divided among the 3 study groups. INTERVENTIONS: In separate conditions, participants were exposed to anger and neutral autobiographical scripts during the positron emission tomography study. Subjective self-report and psychophysiologic data were also collected. MAIN OUTCOME MEASURES: Voxelwise methods were used for analyses of regional cerebral blood flow changes for the anger vs neutral contrast within and between groups. RESULTS: Controls showed significantly (P<.001) greater regional cerebral blood flow increases in the left ventromedial prefrontal cortex during anger induction than patients with MDD + A, whereas these differences were not present in other between-group analyses. Also, in controls, an inverse relationship was demonstrated between regional cerebral blood flow changes during anger induction in the left ventromedial prefrontal cortex and left amygdala, whereas in patients with MDD + A there was a positive correlation between these brain regions during anger induction. There was no significant relationship between these brain regions during anger induction in patients with MDD - A. CONCLUSION: These results suggest a pathophysiology of MDD + A that is distinct from that of MDD - A and that may be responsible for the unique clinical presentation of patients with MDD + A.

Adult↗

PubMed1988

Stressful environmental stimuli increase extracellular DOPAC levels in the prefrontal cortex of hypoemotional (Roman high-avoidance) but not hyperemotional (Roman low-avoidance) rats. An in vivo voltammetric study.

The effects of a variety of stressful environmental situations on dopamine metabolism in the prefrontal cortex (as assessed by in vivo voltammetry with carbon fiber electrodes) have been compared in two genetically selected lines of rat (Roman high (RHA/Verh) and low (RLA/Verh) avoidance) which differ drastically in their level of emotionality. Heart rate was continuously monitored in these animals (via chronically implanted subcutaneous electrodes) so as to index the emotional reaction to the stressors. An electrochemical signal corresponding to the oxidation of dihydroxyphenylacetic acid (DOPAC) was recorded in the deeper laminae of the anteromedial prefrontal cortex in both lines of rats. Under normal conditions, this signal was stable for at least 4 h and its amplitude was similar in both lines. Introduction of the animals into an unfamiliar environment (30 min), application of a mild tail pinch (10 min) or of a high-intensity loud noise (30 min) or immobilization (20 min) were all associated with an increase in extracellular cortical DOPAC levels in the hypoemotional RHA/Verh line but not in the hyperemotional RLA/Verh line. Similarly, forced locomotion on a rotarod (40 min) provoked a dramatic increase in the amplitude of the cortical DOPAC oxidation peak in RHA/Verh rats and only a mild increase in this parameter in RLA/Verh rats. In RHA/Verh rats, tolerance to this increase was observed when animals were subjected to forced locomotion every day for 5 days. All of the stressful situations investigated provoked an immediate augmentation of heart rate which resumed gradually after cessation of the stressful stimulus; the magnitude and duration of this increase were much greater in RLA/Verh than in RHA/Verh rats. Moreover, in all stress situations, RLA/Verh but not RHA/Verh rats showed behavioral signs of emotional response e.g. defecation, freezing and self-grooming. It is concluded that the increase in cortical dopamine metabolism induced by stress is not connected to the emotional reaction caused by the aversive nature of the stressor but may rather reflect a heightened attention of the animal or activation of cognitive processes in an attempt to cope with the stressor.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1997

Effects of electrolytic lesions of the medial prefrontal cortex or its subfields on 4-arm baited, 8-arm radial maze, two-way active avoidance and conditioned fear tasks in the rat.

The present study tested the effects of electrolytic lesions in two mPFC subregions, the dorsal anterior cingulate area (dACA) and prelimbic cortex, as well as the effects of a larger medial prefrontal cortex (mPFC) lesion which included both subregions, on 4-arm baited, 4-arm unbaited, 8-arm radial maze task and its reversal (Experiments 1 and 4), two-way active avoidance (Experiments 2 and 5) and conditioned emotional response (Experiments 3 and 6). Rats with large or small lesions of the mPFC learned the location of the 4 baited arms in the training and reversal stages of the radial maze task similarly to sham rats, indicating that these lesions did not affect animals' capacity to process and remember spatial information. dACA and mPFC lesions produced a transient deficit in the acquisition of the radial maze task, suggestive of an involvement of these regions in mnemonic processes. However, in view of the normal performance of these groups by the end of training and during reversal, this deficit is better interpreted as stemming from a difficulty to learn the memory-based strategy used to solve the task. Only mPFC lesion led to better avoidance performance at the beginning of training and tended to increase response during the presentation of a stimulus previously paired with shock, compared to sham rats. Both effects can be taken as an indication of reduced emotionality following mPFC lesion. The results are discussed in relation to known behavioral functions of the mPFC and the suggested functional specialization within this region.

Animals↗

PubMed2006

Interactions among the medial prefrontal cortex, hippocampus and midline thalamus in emotional and cognitive processing in the rat.

The medial prefrontal cortex (mPFC) participates in several higher order functions including selective attention, visceromotor control, decision making and goal-directed behaviors. We discuss the role of the infralimbic cortex (IL) in visceromotor control and the prelimbic cortex (PL) in cognition and their interactions in goal-directed behaviors in the rat. The PL strongly interconnects with a relatively small group of structures that, like PL, subserve cognition, and together have been designated the 'PL circuit.' These structures primarily include the hippocampus, insular cortex, nucleus accumbens, basolateral nucleus of the amygdala, the mediodorsal and reuniens nuclei of the thalamus and the ventral tegmental area of the midbrain. Lesions of each of these structures, like those of PL, produce deficits in delayed response tasks and memory. The PL (and ventral anterior cingulate cortex) (AC) of rats is ideally positioned to integrate current and past information, including its affective qualities, and act on it through its projections to the ventral striatum/ventral pallidum. We further discuss the role of nucleus reuniens of thalamus as a major interface between the mPFC and the hippocampus, and as a prominent source of afferent limbic information to the mPFC and hippocampus. We suggest that the IL of rats is functionally homologous to the orbitomedial cortex of primates and the prelimbic (and ventral AC) cortex to the lateral/dorsolateral cortex of primates, and that the IL/PL complex of rats exerts significant control over emotional and cognitive aspects of goal-directed behavior.

Animals↗

PubMed2005

Angiotensinase activity is asymmetrically distributed in the amygdala, hippocampus and prefrontal cortex of the rat.

There are important asymmetries in brain functions such as emotional processing and stress response in humans and animals. Knowledge of the bilateral distribution of brain neurotransmitters is important to appropriately understand its functions. Some peptides such as those included in the renin-angiotensin system (RAS) and cholecystokinin (CCK) are related to modulation of behavior and stress. However, although angiotensin AT1 and CCK type 2 receptors were found in adult rat brain, there are no studies of their bilateral distribution in stress-related areas. The function of angiotensin peptides is depending on the action of several aminopeptidases (AP) called angiotensinases, some of them being also involved in the metabolism of CCK. We have studied the bilateral distribution of soluble (SOL) and membrane-bound (MEM) alanyl- (AlaAP), cystinyl- (CysAP), glutamyl- (GluAP) and aspartyl- (AspAP) AP activities in stress-related areas such as amygdala, hippocampus and medial prefrontal cortex of adult male rats in resting conditions. These enzymes are involved in the metabolism of angiotensins (AlaAP, CysAP, GluAP, AspAP) and CCK (GluAP, AspAP). In the amygdala, all the activities studied showed a right predominance with a significant difference ranging from 30% for SOL CysAP to 125% for SOL GluAP. In the hippocampus, there was a left predominance for SOL AlaAP, SOL and MEM CysAP and MEM AspAP activities (100, 80, 300 and 100% higher, respectively). In contrast, GluAP predominated remarkably in the right hippocampus (eight-fold for SOL and three-fold for MEM). In the prefrontal cortex, SOL and MEM CysAP and SOL AspAP predominated in the left hemisphere (40, 100 and 40% higher, respectively). These results demonstrated a heterogeneous bilateral pattern of angiotensinase activities in motivation and stress-related areas. This may reflect an uneven asymmetrical distribution of their endogenous substrates depending on the brain location and consequently, it would be also a reflect of the asymmetries in the functions they are involved in.

Aminopeptidases↗

PubMed2002

Enhanced motivation to self-administer cocaine is predicted by self-grooming behaviour and relates to dopamine release in the rat medial prefrontal cortex and amygdala.

Rats, like humans, show strong individual differences in their response to anxiogenic and stressful stimuli. In the present study we evaluated whether differences in stress-induced self-grooming behaviour may predict an individual's vulnerability to engage in drug self-administration behaviour. From a population of Wistar rats, the lower and upper quartile with respect to time spent self-grooming on an elevated plus maze (EPM) were selected and trained to intravenously self-administer cocaine under fixed and progressive ratio schedules of reinforcement. High grooming (HG) rats reached considerably higher breakpoints than low grooming (LG) rats but showed no differences in acquisition rate and dose-response relationships. Further, EPM exposure elicited higher anxiety levels and enhanced plasma corticosterone secretion in HG rats. In addition, HG rats did not display enhanced novelty-seeking and still spent more time self-grooming during an EPM re-test following the cocaine self-administration procedure, indicating that stress-induced self-grooming is a stable behavioural trait marker. Neurochemically, electrically evoked [(3)H]dopamine release in vitro was profoundly lower in brain slices from the substantia nigra, medial prefrontal cortex and amygdala of naive HG rats as compared to LG rats, whereas no differences were found in the nucleus accumbens shell and core, the ventral tegmental area and caudate putamen. In conclusion, stress-induced self-grooming specifically predicts enhanced motivation to self-administer cocaine rather than sensitivity to its reinforcing effects. Responsiveness of dopaminergic nerve terminals in the medial prefrontal cortex and amygdala may represent pre-existing underlying factors.

Amygdala↗

PubMed2002

Projections from the parahippocampal region to the prefrontal cortex in the rat: evidence of multiple pathways.

The purpose of the present study was to investigate, by means of anterograde tracing methods, the detailed organization of the parahippocampal-prefrontal projections in the rat brain. Efferents from the perirhinal cortex were found to terminate principally in both the ventromedial (prelimbic and infralimbic cortices) and lateral (agranular insular cortex) regions of the prefrontal cortex. Terminal fields were observed mainly in the superficial layers of the prefrontal cortex. Projections arising from the dorsolateral entorhinal cortex, which borders the perirhinal cortex along its ventral extent, were similarly directed to the ventromedial and lateral prefrontal cortices but also encompassed other frontal areas (dorsomedial and orbital prefrontal regions). Terminal fields of entorhinal projections were also found in the superficial layers of the prefrontal cortex. A third pathway, taking its source in the post-rhinal cortex, presented striking topographical differences with the two other output systems. Hence, post-rhinal efferences terminated only in the ventrolateral orbital area. The results indicate that two main routes originate from the parahippocampal region to reach the prefrontal cortex. One pathway involves the rostral and lateral portions of the parahippocampal region (perirhinal and dorsolateral entorhinal cortices), and the other relies on its most caudal region, the post-rhinal cortex. The presence of such different multiple parahippocampal-prefrontal pathways may have functional relevance for learning and memory processes.

Animals↗

PubMed1995

Long-term effects of chronic social stress on serotonergic indices in the prefrontal cortex of adult male cynomolgus macaques.

We examined the effects of chronic social stress and social rank on monamine concentrations in the prefrontal cortex (PFC) in adult male cynomolgus macaques (Macaca fascicularis). Seventy-five animals were housed in five-member social groups for 28 months and were exposed to three experimental conditions. A 'no-stress' condition was comprised of animals housed in groups of stable membership throughout the study. Animals assigned to a 'past-stress' condition had their group memberships reorganized at monthly intervals during the first (but not last) 14 months of the study, and a third 'recent-stress' condition consisted of social groups reorganized only during the last 14 months. At necropsy, the brains were collected and frozen at -70 degrees C until analyzed. Prefrontal orbital cortex was assayed for monoamines (serotonin (5-HT), dopamine (DA), norepinephrine (NE)), metabolites (5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), 3-methoxy-4-hydroxyphenethyleneglycol (MHPG)), and tryptophan using high-performance liquid chromatography with electrochemical detection. Animals in the past-stress condition had significantly lower PFC 5-HIAA concentrations compared to those in the no-stress condition (P < 0.05). PFC 5-HT concentrations of animals in the past-stress condition were significantly lower than those in the no-stress and recent-stress conditions (P < 0.01). The concentrations of DA, HVA, NE and MHPG were not altered. These data suggest that exposure to chronic social stress is associated with long-term selective reductions in serotonergic activity in the PFC. This effect may underlie the association in human beings between reduced serotonergic function and conditions such as pathological grief and posttraumatic stress disorder.

Animals↗

PubMed2002

Extracellular serotonin in the prefrontal cortex is limited through terminal 5-HT(1B) autoreceptors: a microdialysis study in knockout mice.

RATIONALE: Serotonin (5-HT) autoreceptors regulate extracellular 5-HT levels and have been suggested to limit the effects of acute treatment with selective serotonin reuptake inhibitors (SSRIs). OBJECTIVES: The role of terminal 5-HT(1B) autoreceptors was assessed by comparing the effects of a SSRI on extracellular 5-HT in wild-type and 5-HT(1B) receptor knockout (KO) mice and by using a 5-HT(1B) receptor antagonist. Since systemic SSRI administration also activates somatodendritic 5-HT(1A) autoreceptors, a SSRI was administered locally to study the role of terminal 5-HT(1B) autoreceptors. METHODS: In vivo microdialysis in wild-type and 5-HT(1B) receptor KO mice was used to study the effects of the 5-HT(1B) receptor agonist CP93129 (1 micro M), the SSRI fluvoxamine (0.3 micro M and 1.0 micro M) and the 5-HT(1B) receptor antagonist NAS-181 (1 micro M) on extracellular 5-HT in the medial prefrontal cortex. RESULTS: The 5-HT increase induced by local SSRI administration was augmented in 5-HT(1B) KO mice relative to wild-type mice and was augmented by simultaneous administration of a 5-HT(1B) receptor antagonist in the latter genotype. Basal 5-HT levels did not differ between the two genotypes. Activation of 5-HT(1B) receptors by CP93129 decreased extracellular 5-HT, whereas 5-HT levels in wild-type mice were not affected by the 5-HT(1B) receptor antagonist NAS-181. In 5-HT(1B) KO mice, NAS-181 did not affect extracellular 5-HT and did not further increase the effect of fluvoxamine, showing that NAS-181 is a selective 5-HT(1B) receptor antagonist. The greater increase in 5-HT levels following combined administration of a SSRI with NAS-181 in wild-type mice, relative to 5-HT(1B) KO mice, suggests possible adaptive changes in the KO mice. CONCLUSIONS: The present study shows that terminal 5-HT(1B) autoreceptors play a significant role in the regulation of 5-HT release in the prefrontal cortex.

Analysis of Variance↗

PubMed2000

Regulation of nonphosphorylated and phosphorylated forms of neurofilament proteins in the prefrontal cortex of human opioid addicts.

The neurofilament (NF) proteins (NF-H, NF-M, and NF-L for high, medium, and low molecular weights) play a crucial role in the organization of neuronal shape and function. In a preliminary study, the abundance of total NF-L was shown to be decreased in brains of opioid addicts. Because of the potential relevance of NF abnormalities in opioid addiction, we quantitated nonphosphorylated and phosphorylated NF in postmortem brains from 12 well-defined opioid abusers who had died of an opiate overdose (heroin or methadone). Levels of NF were assessed by immunoblotting techniques using phospho-independent and phospho-dependent antibodies, and the relative (% changes in immunoreactivity) and absolute (changes in ng NF/microg total protein) amounts of NF were calculated. Decreased levels of nonphosphorylated NF-H (42-32%), NF-M (14-9%) and NF-L (30-29%) were found in the prefrontal cortex of opioid addicts compared with sex, age, and postmortem delay-matched controls. In contrast, increased levels of phosphorylated NF-H (58-41%) and NF-M (56-28%) were found in the same brains of opioid addicts. The ratio of phosphorylated to nonphosphorylated NF-H in opioid addicts (3.4) was greater than that in control subjects (1.6). In the same brains of opioid addicts, the levels of protein phosphatase of the type 2A were found unchanged, which indicated that the hyperphosphorylation of NF-H is not the result of a reduced dephosphorylation process. The immunodensities of GFAP (the specific glial cytoskeletol protein), alpha-internexin (a neuronal filament related to NF-L) and synaptophysin (a synapse-specific protein) were found unchanged, suggesting a lack of gross changes in glial reaction, other intermediate filaments of the neuronal cytoskeletol, and synaptic density in the prefrontal cortex of opioid addicts. These marked reductions in total NF proteins and the aberrant hyperphosphorylation of NF-H in brains of opioid addicts may play a significant role in the cellular mechanisms of opioid addiction.

Adult↗

PubMed2004

In vivo excitation of GABA interneurons in the medial prefrontal cortex through 5-HT3 receptors.

Serotonin (5-hydroxytryptamine, 5-HT) controls pyramidal cell activity in prefrontal cortex (PFC) through various receptors, in particular, 5-HT1A and 5-HT2A receptors. Here we report that the physiological stimulation of the raphe nuclei excites local, putatively GABAergic neurons in the prelimbic and cingulate areas of the rat PFC in vivo. These excitations had a latency of 36 +/- 4 ms and a duration of 69 +/- 9 ms and were blocked by the i.v. administration of the 5-HT3 receptor antagonists ondansetron and tropisetron. The latency and duration were shorter than those elicited through 5-HT2A receptors in pyramidal neurons of the same areas. Double in situ hybridization histochemistry showed the presence of GABAergic neurons expressing 5-HT3 receptor mRNA in PFC. These cells were more abundant in the cingulate, prelimbic and infralimbic areas, particularly in superficial layers. The percentages of GAD mRNA-positive neurons expressing 5-HT3 receptor mRNA in prelimbic cortex were 40, 18, 6 and 8% in layers I, II-III, V and VI, respectively, a distribution complementary to that of cells expressing 5-HT2A receptors. Overall, these results support an important role of 5-HT in the control of the excitability of apical dendrites of pyramidal neurons in the medial PFC through the activation of 5-HT3 receptors in GABAergic interneurons.

Animals↗

PubMed2003

Stimulation of alpha1-adrenoceptors in the rat medial prefrontal cortex increases the local in vivo 5-hydroxytryptamine release: reversal by antipsychotic drugs.

Pyramidal neurons of the medial prefrontal cortex (mPFC) project to midbrain serotonergic neurons and control their activity. The stimulation of prefrontal 5-HT2A and AMPA receptors increases pyramidal and serotonergic cell firing, and 5-hydroxytryptamine (5-HT) release in mPFC. As the mPFC contains abundant alpha1-adrenoceptors whose activation increases the excitability of pyramidal neurons, we examined the effects of their stimulation on local 5-HT release, using microdialysis. The application of the alpha1-adrenoceptor agonist cirazoline by reverse dialysis increased the prefrontal 5-HT release in a concentration-dependent manner, an effect antagonized by coperfusion of TTX, prazosin (alpha1-adrenoceptor antagonist), BAY x 3702 (5-HT1A agonist), NBQX (AMPA/KA antagonist) and 1S,3S-ACPD (mGluR II/III agonist), but not by MK-801 (NMDA antagonist). Cirazoline also enhanced the increase in 5-HT release induced by DOI (5-HT2A/2C agonist) and AMPA. In addition, M100907 (5-HT2A antagonist) but not SB-242084 (5-HT2C antagonist) reversed the cirazoline- and AMPA-induced 5-HT release. These results suggest that the stimulation of prefrontal alpha1-adrenoceptors activates pyramidal afferents to ascending serotonergic neurons. The effect of cirazoline was also reversed by coperfusion of classical (chlorpromazine, haloperidol) and atypical (clozapine, olanzapine) antipsychotics, which suggests that a functional antagonism of the alpha1-adrenoceptor-mediated activation of prefrontal neurons may partly underlie their therapeutic action.

Adrenergic alpha-Agonists↗

PubMed2004

Analogical reasoning and prefrontal cortex: evidence for separable retrieval and integration mechanisms.

The present study examined the contributions of prefrontal cortex (PFC) subregions to two component processes underlying verbal analogical reasoning: semantic retrieval and integration. Event-related functional magnetic resonance imaging data were acquired while subjects performed propositional analogy and semantic decision tasks. On each trial, subjects viewed a pair of words (pair 1), followed by an instructional cue and a second word pair (pair 2). On analogy trials, subjects evaluated whether pair 2 was semantically analogous to pair 1. On semantic trials, subjects indicated whether the pair 2 words were semantically related to each other. Thus, analogy--but not semantic--trials required integration across multiple retrieved relations. To identify regions involved in semantic retrieval, we manipulated the associative strength of pair 1 words in both tasks. Anterior left inferior PFC (aLIPC) was modulated by associative strength, consistent with a role in controlled semantic retrieval. Left frontopolar cortex was insensitive to associative strength, but was more sensitive to integration demands than was aLIPC, consistent with a role in integrating the products of semantic retrieval to evaluate whether distinct representations are analogous. Right dorsolateral PFC exhibited a profile consistent with a role in response selection rather than retrieval or integration. These findings indicate that verbal analogical reasoning depends on multiple, PFC-mediated computations.

Adult↗

PubMed2001

Effects of rat medial prefrontal cortex temporal inactivation on a delayed alternation task.

To determine the involvement of the medial prefrontal cortex (mPFC) in operant-type delayed alternation, microinjections of muscimol into the mPFC were used for temporal inactivation during behavioral tests in rats. The temporal mPFC inactivation showed effects related to both dorsal (decreased delay-dependent correct ratio, indicating working memory-related deficits) and ventral hippocampus inactivation (increased tendency to repeat errors) reported in our recent paper, without motor or sensory effects. These findings suggest that the mPFC integrates information from different hippocampal regions during a delayed alternation task.

Animals↗

PubMed2003

Significance of dopamine transmission in the rat medial prefrontal cortex for conditioned fear.

Previous studies have demonstrated activation of dopamine transmission in the medial prefrontal cortex (mPFC) by conditioned fear stimuli. Therefore, the present study investigated the functional significance of mPFC dopamine for a conditioned fear response to a tone. We examined the effects of inhibition or stimulation of mPFC dopamine transmission by local microinfusion of the D1/D2-receptor antagonist cis-flupenthixol or the indirect dopamine receptor agonist D-amphetamine, respectively, in a classical fear-conditioning paradigm in Wistar rats. Rats received tone-shock pairings and were later exposed to the tone alone. Freezing was used as measure of conditioned fear. Presence of the drugs in the mPFC during the tone-shock pairings did not affect freezing during subsequent presentation of the tone alone. However, when cis-flupenthixol and D-amphetamine were present in the mPFC during presentation of the tone alone, freezing to the tone was reduced. We demonstrated that the decreased freezing could be explained neither by state dependency nor infusion-induced alterations in activity. Our data indicate that mPFC dopamine transmission is important for the retrieval/expression, but not the formation, of conditioned fear. The reduction of conditioned fear by prefrontal infusion of both cis-flupenthixol and D-amphetamine may reflect normal expression of conditioned fear requires an optimal level of mPFC dopamine activity.

Animals↗