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Results for “Prefrontal Cortex”

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PubMed2001

Dopamine D1/D5 receptor modulation of excitatory synaptic inputs to layer V prefrontal cortex neurons.

Dopamine acts mainly through the D1/D5 receptor in the prefrontal cortex (PFC) to modulate neural activity and behaviors associated with working memory. To understand the mechanism of this effect, we examined the modulation of excitatory synaptic inputs onto layer V PFC pyramidal neurons by D1/D5 receptor stimulation. D1/D5 agonists increased the size of N-methyl-d-aspartate (NMDA) component of excitatory postsynaptic currents (EPSCs) through a postsynaptic mechanism. In contrast, D1/D5 agonists caused a slight reduction in the size of the non-NMDA component of EPSCs through a small decrease in release probability. With 20 Hz synaptic trains, we found that the D1/D5 agonists increased depolarization of summating the NMDA component of excitatory postsynaptic potential (EPSP). By increasing the NMDA component of EPSCs, yet slightly reducing release, D1/D5 receptor activation selectively enhanced sustained synaptic inputs and equalized the sizes of EPSPs in a 20-Hz train.

Animals↗

PubMed1995

Semantic encoding and retrieval in the left inferior prefrontal cortex: a functional MRI study of task difficulty and process specificity.

Prefrontal cortical function was examined during semantic encoding and repetition priming using functional magnetic resonance imaging (fMRI), a noninvasive technique for localizing regional changes in blood oxygenation, a correlate of neural activity. Words studied in a semantic (deep) encoding condition were better remembered than words studied in both easier and more difficult nonsemantic (shallow) encoding conditions, with difficulty indexed by response time. The left inferior prefrontal cortex (LIPC) (Brodmann's areas 45, 46, 47) showed increased activation during semantic encoding relative to nonsemantic encoding regardless of the relative difficulty of the nonsemantic encoding task. Therefore, LIPC activation appears to be related to semantic encoding and not task difficulty. Semantic encoding decisions are performed faster the second time words are presented. This represents semantic repetition priming, a facilitation in semantic processing for previously encoded words that is not dependent on intentional recollection. The same LIPC area activated during semantic encoding showed decreased activation during repeated semantic encoding relative to initial semantic encoding of the same words. This decrease in activation during repeated encoding was process specific; it occurred when words were semantically reprocessed but not when words were nonsemantically reprocessed. The results were apparent in both individual and averaged functional maps. These findings suggest that the LIPC is part of a semantic executive system that contributes to the on-line retrieval of semantic information.

Adolescent↗

PubMed2006

One session of high frequency repetitive transcranial magnetic stimulation (rTMS) to the right prefrontal cortex transiently reduces cocaine craving.

BACKGROUND: Cocaine dependence is a public health problem affecting 2 million individuals in USA. Craving is a predictor of subsequent cocaine use and is related to changes in brain activity in networks involving the prefrontal cortex. METHODS: We investigated the efficacy of one session of high frequency repetitive transcranial magnetic stimulation (rTMS) to reduce craving in cocaine addicted subjects. Six patients underwent two sessions of 10Hz rTMS over left or right dorsolateral prefrontal cortex (DLPFC). Before, immediately after and 4h after rTMS we measured craving using visual analogue scales. RESULTS: Right, but not left, DLPFC stimulation significantly reduced craving over time (F(2,10)=11.07, p=0.0029). The reduction was 19% (13.4-24.6%) from baseline and disappeared after 4h. The interaction of time by site of stimulation for craving was also significant (F(2,25)=6.13, p=0.0068). CONCLUSION: One session of 10Hz rTMS over right, but not left, DLPFC transiently reduces craving in cocaine dependent individuals. These results highlight the potential of non-invasive neuromodulation as a therapeutic tool for cocaine addiction.

Adult↗

PubMed2004

Effects of environmental enrichment on behavior and dopamine transporter function in medial prefrontal cortex in adult rats prenatally treated with cocaine.

The present study determined if environmental enrichment modifies the effects of prenatal cocaine on open field activity, social interaction and dopamine transporter (DAT) function in the medial prefrontal cortex (mPFC) in rats. Cocaine (40 mg/kg) or saline was administered (s.c.) to pregnant dams from gestation days 8 to 20 (PCOC and PSAL, respectively). At postnatal day 25 (PND 25), female offspring from PCOC and PSAL groups were assigned to the enriched condition (EC; PCOC/EC and PSAL/EC) or impoverished condition (IC; PCOC/IC and PSAL/IC). On PND 60, 90 and 120, locomotor activity, rearing behavior and social interactions were assessed in the open field. On PND 345, rats were anesthetized, challenged with nicotine (0.4 mg/kg), and DAT function in medial prefrontal cortex (mPFC) was assessed using in vivo voltammetry. EC groups displayed decreased locomotor activity across test days, while activity in IC groups did not habituate across days. Generally, PCOC groups displayed more rearing behavior than PSAL groups. During social interaction assessment, IC groups followed their social partner more frequently than EC groups. Moreover, the PCOC/IC group initiated more play solicitations and was engaged in mutual rearing less frequently than PCOC/EC, PSAL/IC and PSAL/EC groups, indicating that epigenetic environmental factors decreased the divergent social behaviors displayed by the PCOC/IC group. Results from in vivo voltammetry experiments demonstrated differences in baseline DAT function in response to environmental enrichment in the prenatal saline groups; however, no effect of prenatal cocaine was observed under baseline conditions. Nicotine challenge unmasked an effect of prenatal cocaine on DA clearance rate in mPFC in the IC groups, which was attenuated by environmental enrichment. Taken together, PCOC/IC rats displayed divergent social interaction and altered DAT function in mPFC, whereas the PCOC/EC group generally was not different from PSAL groups, suggesting that environmental enrichment attenuates the behavioral and neurochemical effects of prenatal cocaine.

Animals↗

PubMed1977

Self-stimulation of the MFB or VTA after microinjection of haloperidol into the prefrontal cortex of the rat.

Haloperidol, a dopamine receptor antagonist, was microinjected in doses of 12 or 24 microng into the prefrontal cortex of the rat. Its effects on self-stimulation of the ventral tegmental area (VTA) or the medial forebrain bundle (MFB) were examined. It was found that these injections failed to attenuate self-stimulation at either structure. However, when haloperidol was injected into the caudate-putamen complex, a decrease in self-stimulation occurred within these structures. These results suggest that dopamine in the medial prefrontal cortex is not necessarily a part of the neurochemical substrate underlying self-stimulation of the ventral tegmental area or medial forebrain bundle.

Animals↗

PubMed2004

Combined unilateral lesions of the amygdala and orbital prefrontal cortex impair affective processing in rhesus monkeys.

The amygdala and orbital prefrontal cortex (PFo) interact as part of a system for affective processing. To assess whether there is a hemispheric functional specialization for the processing of emotion or reward or both in nonhuman primates, rhesus monkeys (Macaca mulatta) with combined lesions of the amygdala and PFo in one hemisphere, either left or right, were compared with unoperated controls on a battery of tasks that tax affective processing, including two tasks that tax reward processing and two that assess emotional reactions. Although the two operated groups did not differ from each other, monkeys with unilateral lesions, left and right, showed altered reward-processing abilities as evidenced by attenuated reinforcer devaluation effects and an impairment in object reversal learning relative to controls. In addition, both operated groups showed blunted emotional reactions to a rubber snake. By contrast, monkeys with unilateral lesions did not differ from controls in their responses to an unfamiliar human (human "intruder"). Although the results provide no support for a hemispheric specialization of function, they yield the novel finding that unilateral lesions of the amygdala-orbitofrontal cortical circuit in monkeys are sufficient to significantly disrupt affective processing.

Affect↗

PubMed1999

Left and right 6-hydroxydopamine lesions of the medial prefrontal cortex differentially affect voluntary ethanol consumption.

Dopaminergic projections to the medial prefrontal cortex (mPFC) were unilaterally lesioned with 6-hydroxydopamine (6-OHDA) to examine how dopamine (DA) asymmetry in the mPFC influences voluntary ethanol consumption. Differences in nucleus accumbens (NAS) DA neurotransmission have been related to individual differences in locomotor activity and in the rewarding efficacy of ethanol. Therefore, differences in locomotor activity were used to further characterize the effects of unilateral mPFC 6-OHDA lesions on ethanol consumption. Male Long Evans rats were assessed for high versus low levels of spontaneous locomotor activity. DA terminals in the left or right mPFC were unilaterally lesioned with 6-OHDA, resulting in an average DA depletion of 54% and 50%, respectively. After a minimum seven-day recovery period, preference for a 10% ethanol solution vs. water was determined in a 24-h 2-bottle home-cage free-choice paradigm. Left mPFC 6-OHDA lesions increased and right lesions decreased ethanol consumption. These differential effects of left and right lesions were primarily attributable to rats exhibiting low locomotor activity prior to surgery. The present data suggest that right greater than left cortical DA asymmetry in combination with low endogenous NAS DA (predicted by low locomotor activity levels) may increase the vulnerability to abuse ethanol.

Alcohol Drinking↗

PubMed1994

Efferent connections of the medial prefrontal cortex in the rabbit.

The different cytoarchitectonic regions of the medial prefrontal cortex (mPFC) have recently been shown to play divergent roles in associative learning in rabbits. To determine if these subareas of the mPFC, including areas 24 (anterior cingulate cortex), 25 (infralimbic cortex), and 32 (prelimbic cortex) have differential efferent connections with other cortical and subcortical areas in the rabbit, anterograde and retrograde tracing experiments were performed using the Phaseolus vulgaris leukoagglutinin (PHA-L), and horseradish peroxidase (HRP) techniques. All three areas showed local dorsal-ventral projections into each of the other areas, and a contralateral projection to the homologous area on the other side of the brain. All three also revealed a trajectory through the striatum, resulting in heavy innervation of the caudate nucleus, the claustrum, and a lighter projection to the agranular insular cortex. The thalamic projections of areas 24 and 32 were similar, but not identical, with projections to the mediodorsal nucleus (MD) and all of the midline nuclei. However, the primary thalamic projections from area 25 were to the intralaminar and midline nuclei. All three areas also projected to the ventromedial and to a lesser extent to the ventral posterior thalamic nuclei. Projections were also observed in the lateral hypothalamus, in an area just lateral to the descending limb of the fornix. Amygdala projections from areas 32 and 24 were primarily to the lateral, basolateral and basomedial nuclei, but area 25 also projected to the central nucleus. All three areas also showed projections to the midbrain periaqueductal central gray, median raphe nucleus, ventral tegmental area, substantia nigra, locus coeruleus and pontine nuclei. However, only areas 24 and the more dorsal portions of area 32 projected to the superior colliculus. Area 25 and the ventral portions of area 32 also showed a bilateral projection to the parabrachial nuclei and dorsal and ventral medulla. The dorsal portions of area 32, and all of area 24 were, however, devoid of these projections. It is suggested that these differential projections are responsible for the diverse roles that the cytoarchitectonic subfields of the mPFC have been demonstrated to play in associative learning.

Animals↗

PubMed2006

Group III metabotropic glutamate receptor agonists selectively suppress excitatory synaptic currents in the rat prefrontal cortex induced by 5-hydroxytryptamine2A receptor activation.

Activation and blockade of prefrontal cortical 5-hydroxytryptamine2A (5-HT2A) receptors have been linked to the action of hallucinogenic and antidepressant/antipsychotic drugs; these effects may involve modulation of glutamate release from thalamocortical afferents. Although activation of metabotropic glutamate 2 (mGlu2) receptors may suppress 5-HT-induced excitatory postsynaptic currents (EPSCs), group III mGlu receptors (mGlu4/7/8) also are expressed in the thalamus and may suppress 5-HT-induced EPSCs. We have found by intracellular recordings from layer V pyramidal cells of the medial prefrontal cortex (mPFC) that group III mGlu receptor agonists (R,S)-4-phosphonophenylglycine (PPG), L-4-phosphono-2-aminobutyric acid (L-AP4), L-serine-O-phosphate (L-SOP), and (S)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP4) preferentially suppress 5-HT-induced EPSCs compared with excitatory postsynaptic potentials evoked by electrical stimulation of the white matter. A number of pharmacological features [e.g., the rank order of agonist potency; MAP4 partial agonist action; differential potency for the group III mGlu receptor antagonist (R,S)-alpha-cyclopropyl-4-phosphonophenylglycine (CPPG) in blocking the suppressant action of PPG or MAP4; and a relatively low potency of 2S-2-amino-2-(1S,2S-2-carboxycycloprop-1-yl)-3(xanthy-9-yl)propanoic acid (LY341495) in blocking the suppressant action of PPG or L-SOP] suggest that activation of both mGlu4 and mGlu8 receptors may play a role in suppressing 5-HT-induced EPSCs. Furthermore, L-SOP did not alter the synaptic currents or steady-state inward current induced by alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid. Thus, although both group III and group II mGlu receptor agonists suppress the frequency of 5-HT-induced EPSCs in the mPFC, they differ in that the group III mGlu receptor agonists appear to have relatively minimal effects on glutamate released by sources other than thalamocortical afferents.

Amino Acids↗

PubMed1999

Changes in serotonin2A and GABA(A) receptors in schizophrenia: studies on the human dorsolateral prefrontal cortex.

Having shown a decrease in serotonin2A receptors in the dorsolateral prefrontal cortex (DLPFC) from schizophrenic subjects, we have now determined if this change was reflective of widespread changes in neurochemical markers in DLPFC in schizophrenia. In Brodmann's area (BA) 9 from 19 schizophrenic and 19 control subjects, we confirmed a decrease in the density of [3H]ketanserin binding to serotonin2A receptors in tissue from the schizophrenic subjects [39 +/- 3.3 vs. 60 +/- 3.6 fmol/mg estimated tissue equivalents (ETE); p < 0.005]. In addition, the density of [3H]muscimol binding to GABA(A) receptors was increased in the schizophrenic subjects (526 +/- 19 vs. 444 +/- 28 fmol/mg ETE; p < 0.02). [3H]YM-09151-2, N-[1-(2-thienyl)cyclohexyl]-3,4-[3H]piperidine, [3H]SCH 23390, [3H]mazindol, and N(G)-nitro-L-[3H]arginine binding to BA 9 did not differ between groups, and there was no specific binding of [3H]raclopride or 7-hydroxy-2-(di-n-[3H]propylamino)tetralin to BA 9 from either cohort of subjects. This suggests the density of dopamine D1-like and NMDA receptors, the dopamine transporter, and nitric oxide synthase activity are not altered in BA 9 from schizophrenic subjects. The selective nature of the changes in serotonin2A and GABA(A) receptors in DLPFC could indicate that these changes are involved in the pathology of schizophrenia.

Adult↗

PubMed2000

Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited.

Evidence implicates subtle neuronal pathology of the prefrontal cortex (PFC) in schizophrenia, but how this pathology is reflected in physiological neuroimaging experiments remains controversial. We investigated PFC function in schizophrenia using functional magnetic resonance imaging (fMRI) and a parametric version of the n-back working memory (WM) task. In a group of patients who performed relatively well on this task, there were three fundamental deviations from the 'healthy' pattern of PFC fMRI activation to varying WM difficulty. The first characteristic was a greater magnitude of PFC fMRI activation in the context of slightly impaired WM performance (i.e. physiological inefficiency). The second was that the significant correlations between behavioral WM performance and dorsal PFC fMRI activation were in opposite directions in the two groups. Third, the magnitude of the abnormal dorsal PFC fMRI response was predicted by an assay of N-acetylaspartate concentrations (NAA) in dorsal PFC, a measure of neuronal pathology obtained using proton magnetic resonance spectroscopy. Patients had significantly lower dorsal PFC NAA than controls and dorsal PFC NAA inversely predicted the fMRI response in dorsal PFC (areas 9, 46) to varying WM difficulty - supporting the assumption that abnormal PFC responses arose from abnormal PFC neurons. These data suggest that under certain conditions the physiological ramifications of dorsal PFC neuronal pathology in schizophrenia includes exaggerated and inefficient cortical activity, especially of dorsal PFC.

Adolescent↗

PubMed2005

Only spontaneous counterfactual thinking is impaired in patients with prefrontal cortex lesions.

Counterfactual thoughts (CFT) are mental simulations of what might have been if another behavior had been executed. They are pervasive in everyday life, help people learn from experience, modulate their emotional state, and contribute to decision-making and social functioning. To test the hypothesis that the prefrontal cortex (PFC) is involved in the generation, content, and use of CFT, we studied 18 patients with strictly prefrontal cortex lesions. Our results indicated that the PFC is crucial only for self-generated counterfactual reflections. We did not detect CFT generation differences based on lesion location within the PFC. CFT performance correlated positively with measures of attention, creativity, verbal skills, conscientiousness, and self-esteem and negatively with depression and dysexecutive symptoms. An impairment in counterfactual thinking may contribute to the lack of regret and insight often observed in patients with frontal lobe lesions.

Adult↗

PubMed2002

Kappa-Opioid and NMDA glutamate receptors are differentially targeted within rat medial prefrontal cortex.

Activation of kappa-opioid receptors (KOR) in the medial prefrontal cortex (mPFC) modulates excitatory transmission, which may involve interactions with N-methyl-D-aspartate (NMDA) glutamate receptors. We investigated possible anatomical correlates of this modulation by using dual labeling electron microscopy to examine the cellular distributions of antibodies raised against KOR and the R1 subunit of the NMDA receptor (NR1). KOR immunoreactivity primarily was localized to plasma and vesicular membranes of axons and axon terminals that were morphologically heterogeneous. A small proportion of KOR immunoreactivity was associated with cytosolic compartments of dendrites and membranes of glial processes. NR1 labeling was mainly postsynaptic, associated most often with membranes of cytoplasmic organelles in cell bodies and large dendrites and plasmalemmal surfaces of distal dendrites. The remaining NR1-labeled profiles were axonal profiles and glial processes. Of all cellular associations between labeled profiles, the majority were KOR-labeled axons that contacted NR1-immunoreactive dendrites or cell bodies. Occasionally the two antigens were colocalized in axon terminals that formed either asymmetric synapses or displayed varicose morphology. KOR and NR1 also were colocalized within dendrites, and rarely were observed in the same cell bodies. Occasionally glial processes coursing adjacent to axo-spinous appositions expressed both KOR and NR1 immunoreactivity. These results indicate that ligand activation of KOR or NMDA receptors differentially modulates excitatory transmission in the mPFC through pre- and postsynaptic mechanisms, respectively. The data also suggest more minor roles for colocalized KOR and NMDA receptors in shared regulation of presynaptic transmitter release, postsynaptic responsivity, and glial function.

Animals↗

PubMed2006

Distinct patterns of plasticity in prefrontal cortex neurons that encode slow and fast responses to stress.

The prefrontal cortex (PFC) has been implicated in cognitive and affective responses to acute and chronic stress; however, direct evidence for the reactivity or adaptability of PFC neurons to stress is lacking. We followed the unit activity of medial PFC (mPFC) neurons in awake rats during two consecutive exposures to restraint stress or to a non-aversive novel object. The majority (75%) of mPFC neurons had significant responses to the initial restraint that was differentiated into one of three temporal patterns: (i) phasic increase in firing rate during the restraint period, (ii) slow onset increase in firing rate that was sustained for > 2 h after restraint, and (iii) brief bi-phasic responses to initiation and termination of restraint. Exposure to a novel object elicited an exposure-locked phasic response in 40% of the neurons. None of the neurons displayed the sustained activation that was prominent after restraint. A second exposure to the object no longer elicited this phasic response while neurons in the three restraint-responsive groups modified their firing rate during the second restraint in a manner that was specific to their pattern of response to the first restraint. These findings demonstrate that whereas some mPFC neurons respond phasically to novel stimuli irrespective of their aversive nature, a separate population of PFC neurons responds to a stressful stimulus with a sustained increase in firing rate that persists in the absence of that stimulus. These neurons may be a substrate for adaptive responses that are necessary for behavioral modification.

Action Potentials↗

PubMed2004

Properties of delay-period neuronal activity in the primate prefrontal cortex during memory- and sensory-guided saccade tasks.

The dorsolateral prefrontal cortex (DLPFC) is involved in visuospatial short-term (or working) memory. Its cellular basis has been widely examined using the delayed-response paradigm in nonhuman primates. Sustained delay-period activity in DLPFC neurons with directional difference (i.e. directional delay-period activity) has been thought to represent visuospatial short-term (or working) memory. However, little is known about the activity of these neurons during a delay period when the sensory input remains. To address this issue, we examined neuronal activity in the DLPFC while macaque monkeys performed a memory-guided saccade (MGS) task and a delayed visually guided saccade (VGS) task. The MGS task required a memory-guided saccade for a remembered target location. The VGS task had the same temporal sequence as the MGS task, but the sensory stimulus remained during the delay period. We found that most of the DLPFC neurons with directional delay-period activity showed sustained activation during the 'delay' period in the VGS task only ('V-neurons', 49%), or in both tasks ('MV-neurons', 46%). Neurons showing directional delay-period activity in the MGS task only ('M-neurons') were only 5% of the DLPFC neurons with directional delay-period activity. These findings indicate that most DLPFC neurons that are active during the delay period are also active when the sensory stimulus remains, suggesting that DLPFC neurons driven by mnemonic information are also driven by sensory input. Such sustained representation of information should have potential utility in flexible cognitive controls of behaviour.

Action Potentials↗

PubMed1997

Activation of glutamatergic neurotransmission by ketamine: a novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex.

Subanesthetic doses of ketamine, a noncompetitive NMDA receptor antagonist, impair prefrontal cortex (PFC) function in the rat and produce symptoms in humans similar to those observed in schizophrenia and dissociative states, including impaired performance of frontal lobe-sensitive tests. Several lines of evidence suggest that ketamine may impair PFC function in part by interacting with dopamine neurotransmission in this region. This study sought to determine the mechanism by which ketamine may disrupt dopaminergic neurotransmission in, and cognitive functions associated with, the PFC. A thorough dose-response study using microdialysis in conscious rats indicated that low doses of ketamine (10, 20, and 30 mg/kg) increase glutamate outflow in the PFC, suggesting that at these doses ketamine may increase glutamatergic neurotransmission in the PFC at non-NMDA glutamate receptors. An anesthetic dose of ketamine (200 mg/kg) decreased, and an intermediate dose of 50 mg/kg did not affect, glutamate levels. Ketamine, at 30 mg/kg, also increased the release of dopamine in the PFC. This increase was blocked by intra-PFC application of the AMPA/kainate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione CNQX. Furthermore, ketamine-induced activation of dopamine release and impairment of spatial delayed alternation in the rodent, a PFC-sensitive cognitive task, was ameliorated by systemic pretreatment with AMPA/kainate receptor antagonist LY293558. These findings suggest that ketamine may disrupt dopaminergic neurotransmission in the PFC as well as cognitive functions associated with this region, in part, by increasing the release of glutamate, thereby stimulating postsynaptic non-NMDA glutamate receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2006

Regional differentiation of the medial prefrontal cortex in regulating adaptive responses to acute emotional stress.

The medial prefrontal cortex (mPFC) is an important neural substrate for integrating cognitive-affective information and regulating the hypothalamo-pituitary-adrenal (HPA) axis response to emotional stress. mPFC modulation of stress responses is effected in part via the paraventricular hypothalamic nucleus (PVH), which houses both autonomic (sympathoadrenal) and neuroendocrine (HPA) effector mechanisms. Although the weight of evidence suggests that mPFC influences on stress-related PVH outputs are inhibitory, discordant findings have been reported, and such work has tended to treat this cortical region as a unitary structure. Here we compared the effects of lesions of the dorsal versus ventral aspects of mPFC, centered in the prelimbic and infralimbic fields, respectively, on acute restraint stress-induced activation of PVH cell groups mediating autonomic and neuroendocrine responses. Lesions to the dorsal mPFC enhanced restraint-induced Fos and corticotropin-releasing factor (CRF) mRNA expression in the neurosecretory region of PVH. Ablation of the ventral mPFC decreased stress-induced Fos protein and CRF mRNA expression in this compartment but increased Fos induction in PVH regions involved in central autonomic control. Repetition of the experiments in rats bearing retrograde tracer deposits to label PVH-autonomic projections confirmed that ventral mPFC lesions selectively increased stress-induced Fos expression in identified preautonomic neurons. Finally, hormonal indices of HPA activation in response to acute stress were augmented after dorsal mPFC lesions and attenuated after ventral mPFC lesions. These results suggest that dorsal and ventral aspects of the mPFC differentially regulate neuroendocrine and autonomic PVH outputs in response to emotional stress.

Acute Disease↗

PubMed2000

Differential effects of discrete subarea-specific lesions of the rat medial prefrontal cortex on amphetamine- and cocaine-induced behavioural sensitization.

The medial prefrontal cortex (mPFC) of the rat is thought to be important for the initiation of behavioural sensitization. Since the mPFC is not a homogenous structure, we attempted to systematically examine the contribution of the different subareas - infralimbic (il), prelimbic (pl), anterior cingulate (cg) - of the mPFC to the induction of sensitization by selectively lesioning these areas or the whole mPFC with quinolinic acid (45 nmol in 0.5 microl). During an initial habituation session only il or whole mPFC lesions reduced spontaneous activity. Lesioned and sham-lesioned animals were then treated every other day with either saline, DL-amphetamine (3 mg/kg), or cocaine (20 mg/kg) for 2 weeks in their home cages and were then challenged with either DL-amphetamine (1.5 mg/kg) or cocaine (10 mg/kg) after 1 day and 2 weeks of withdrawal. None of the lesions affected the development of amphetamine-induced sensitization in any way, as assessed by several behavioural parameters including locomotion and sniffing. In contrast, cocaine-induced sensitization was significantly attenuated by pl and whole mPFC lesions, while il and cg lesions were without effect. These results show a double dissociation of the role of the mPFC in behavioural sensitization. The mPFC seems to be important only for cocaine- but not for amphetamine-induced sensitization, and only the pl area appears to be of relevance for cocaine-induced sensitization. It is suggested that these differences are due to differences in the pharmacological interaction of cocaine and amphetamine with the mesocortical dopamine system, and to the particular anatomical connections of each of the mPFC subregions.

Amphetamine↗