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PubMed1997

Down-regulation of the D1 and D5 dopamine receptors in the primate prefrontal cortex by chronic treatment with antipsychotic drugs.

D2 dopamine receptor antagonism is postulated to be the key to antipsychotic efficacy in the treatment of schizophrenia. Yet the D1 dopamine family of receptors is far more prevalent in the cortical areas of the brain, such as the prefrontal cortex, which have frequently been implicated in schizophrenia. Moreover, the prefrontal cortical D1 sites have recently been shown to be down-regulated by chronic treatment with several commonly used antipsychotic drugs (Lidow and Goldman-Rakic, 1994). To provide further insight into the pharmacological regulation of the D1 class of dopaminergic receptors, we have now used ribonuclease protection assays to examine the regulation of D1 and D5 dopamine receptor mRNAs in the prefrontal cortex and the neostriatum of nonhuman primates after chronic treatment with eight different drugs representing a wide structural and pharmacological spectrum of antipsychotic medications. The medications were administered for 6 months twice daily at doses that fall within the therapeutic range recommended for human patients. The study also included a substituted benzamide, tiapride, which is a D2 antagonist like the eight aforementioned drugs but reportedly lacks antipsychotic activity. Remarkably, all drugs used in this study, including tiapride, down-regulated the levels of both D1 and D5 mRNAs in the prefrontal cortex by 30% to 60% compared with a vehicle control group, whereas mRNAs in the neostriatum were not affected. This observation indicates that a reduction in the levels of prefrontal cortical dopamine receptors of the D1 class may be an obligatory consequence of D2 receptor antagonism and thus may be a pharmacological property of antipsychotic drugs.

Animals↗
PubMed1983

Putative amino acid neurotransmitters and the nucleus dorsomedialis thalamus-prefrontal cortex pathway in the rat.

Endogenous levels of putative amino acid neurotransmitters (glycine, glutamic acid, aspartic acid, and GABA) in medial and sulcal prefrontal cortex of the rat were analyzed using gas liquid chromatography. No changes were found in the levels of these amino acids in medial and sulcal prefrontal cortex after lesion of the nucleus dorsomedialis of the thalamus suggesting, therefore, that the NDMT-prefrontal cortex pathway is not mediated by these amino acids.

Amino Acids↗
PubMed2001

Dendritic reorganization in pyramidal neurons in medial prefrontal cortex after chronic corticosterone administration.

Chronic stress produces deficits in cognition accompanied by alterations in neural chemistry and morphology. For example, both stress and chronic administration of corticosterone produce dendritic atrophy in hippocampal neurons (Woolley C, Gould E, McEwen BS. 1990. Exposure to excess glucocorticoids alters dendritic morphology of adult hippocampal pyramidal neurons. Brain Res 531:225-231; Watanabe Y, Gould E, McEwen BS, 1992b. Stress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons. Brain Res 588:341-345). Prefrontal cortex is also a target for glucocorticoids involved in the stress response (Meaney MJ, Aitken DH. 1985. [(3)H]Dexamethasone binding in rat frontal cortex. Brain Res 328:176-180); it shows neurochemical changes in response to stress (e.g., Luine VN, Spencer RL, McEwen BS. 1993. Effect of chronic corticosterone ingestion on spatial memory performance and hippocampal serotonergic function. Brain Res 616:55-70; Crayton JW, Joshi I, Gulati A, Arora RC, Wolf WA. 1996. Effect of corticosterone on serotonin and catecholamine receptors and uptake sites in rat frontal cortex. Brain Res 728:260-262; Takao K, Nagatani T, Kitamura Y, Yamawaki S. 1997. Effects of corticosterone on 5-HT(1A) and 5-HT(2) receptor binding and on the receptor-mediated behavioral responses of rats. Eur J Pharmacol 333:123-128; Sandi C, Loscertales M. 1999. Opposite effects on NCAM expression in the rat frontal cortex induced by acute vs. chronic corticosterone treatments. Brain Res 828:127-134), and mediates many of the behaviors that are altered by chronic corticosterone administration (e.g., Lyons DM, Lopez JM, Yang C, Schatzberg AF. 2000. Stress-level cortisol treatment impairs inhibitory control of behavior in monkeys. J Neurosci 20:7816-7821). To determine if glucocorticoid-induced morphological changes also occur in medial prefrontal cortex, the effects of chronic corticosterone administration on dendritic morphology in this corticolimbic structure were assessed. Adult male rats received s.c. injections of either corticosterone (10 mg in 250 microL sesame oil; n = 8) or vehicle (250 microL; n = 8) daily for 3 weeks. A third group of rats served as intact controls (n = 4). Brains were stained using a Golgi-Cox procedure and pyramidal neurons in layer II-III of medial prefrontal cortex were drawn; dendritic morphology was quantified in three dimensions. Sholl analyses demonstrated a significant redistribution of apical dendrites in corticosterone-treated animals: the amount of dendritic material proximal to the soma was increased relative to intact rats, while distal dendritic material was decreased relative to intact animals. Thus, chronic glucocorticoid administration dramatically reorganized apical arbors in medial prefrontal cortex. This reorganization likely reflects functional changes and may contribute to stress-induced changes in cognition.

Animals↗
PubMed2002

[(3)H]cAMP binding sites and protein kinase a activity in the prefrontal cortex of suicide victims.

OBJECTIVE: The cAMP-dependent enzyme protein kinase A phosphorylates intracellular proteins upon activation and thereby plays a major role in mediating various physiological functions in the brain. To examine the role of this enzyme in suicidal behavior, the authors examined the catalytic and regulatory activities of protein kinase A in the postmortem brain of suicide victims. METHOD: Brain tissues were collected from 17 suicide victims and 17 nonpsychiatric comparison subjects. Regulatory activity was determined by examining [(3)H]cAMP binding to protein kinase A, while catalytic activity was determined by enzymatic assay in the presence (total activity) and the absence (endogenous activity) of cAMP in the membrane and cytosol fractions of the prefrontal cortex. RESULTS: The number (B(max)) of [(3)H]cAMP binding sites to protein kinase A was significantly lower in the suicide victims without any changes in affinity in either the membrane or cytosol fractions of the prefrontal cortex. Further, significantly less protein kinase A activity, both in the presence and the absence of cAMP, was seen in the membrane and cytosol fractions of the prefrontal cortex of suicide victims; however, the difference in total protein kinase A activity was much more pronounced. CONCLUSIONS: The results suggest that cAMP binding to the regulatory subunits of protein kinase A, as well as the phosphotransfer catalytic activity of protein kinase A, are lower in the prefrontal cortex of suicide victims than in nonpsychiatric comparison subjects, which may be of clinical relevance in the pathophysiology of suicidal behavior.

Adult↗
PubMed1995

[The neurophysiological correlates of improvement in the cognitive characteristics of monkeys with modification of the NMDA-ergic structures of the prefrontal cortex].

The effect of the NMDA glutamate agonist on cognitive characteristics and short-term memory (SM) was studied in rhesus monkeys. The NMDA effect manifested itself in doubling the SM term and in changing of the unit activity in the prefrontal cortex. The NMDA also induced a considerable increase in the cross-correlation coefficients between the unit responses in visual and prefrontal cortex. The data obtained suggest that the glutamatergic structures of prefrontal cortex take part in the processes of visual recognition and the SM in monkeys. The effect seems to improve the short-term memorizing of a visual information.

Animals↗
PubMed1993

Intracranial cocaine self-administration into the medial prefrontal cortex increases dopamine turnover in the nucleus accumbens.

Adult male rats were trained to intracranially self-administer cocaine (50-100 pmol/100 nl infusion) into the medial prefrontal cortex and to simultaneously deliver an infusion of vehicle (100 nl of artificial cerebrospinal fluid) to a littermate control. When stable base lines of responding were obtained, each rat was implanted with an indwelling jugular catheter for the administration of radioactive precursors for the biogenic amine neurotransmitters. When stable rates of responding were re-established, the animals were infused with the radiolabeled precursors at the beginning of the behavioral session and were sacrificed 60 or 90 min later. Discrete response-contingent infusions of cocaine into the medial prefrontal cortex resulted in decreases in the turnover of dopamine and serotonin and increases in norepinephrine utilization at the site of self-injection compared to vehicle-infused controls. In contrast, DA turnover was significantly increased in the ipsilateral nucleus accumbens of the self-administering rats. These data demonstrate that discrete response-contingent cocaine infusions into the medial prefrontal cortex activate DA innervations of the nucleus accumbens, likely through descending pathways affecting A10 dopaminergic cell bodies, suggesting that neuronal activity similar to that observed after i.v. self-administration is initiated with the ICSA of the drug.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2000

Gender and age-related variation in adenylyl cyclase activity in the human prefrontal cortex, hippocampus and dorsal raphe nuclei.

The influence of gender and age on adenylyl cyclase activity was investigated, through a Dowex-alumina double step chromatographic procedure, in the prefrontal cortex, hippocampus and dorsal raphe nuclei obtained from autopsy cadavers. Results showed that forskolin-stimulated enzyme activity in raphe nuclei was greater in men than in women; a region-dependent rank order of basal, forskolin-induced adenylyl cyclase activity and percentage forskolin-stimulation was observed in women only. Lastly, basal values correlated positively with forskolin-stimulated adenylyl cyclase activity in all areas except the prefrontal cortex of the male subjects. Positive significant correlations were also found between both forskolin-stimulated enzyme activity and percentage forskolin stimulation and aging in the prefrontal cortex. Overall, the findings suggest that sex and/or age-related differences in brain adenylyl cyclase vary from one cerebral region to the other.

Adenylyl Cyclases↗
PubMed2006

A sensitizing regimen of amphetamine impairs visual attention in the 5-choice serial reaction time test: reversal by a D1 receptor agonist injected into the medial prefrontal cortex.

Exposure to repeated, intermittent, escalating doses of amphetamine in rats disrupts information processing in several tasks. Some of these deficits, notably impaired attentional set shifting, may reflect altered prefrontal cortex function. This study examined the effects of repeated treatment with amphetamine on performance in the 5-choice serial reaction time test. This test measures sustained visual attention, a behavior that is known to require the prefrontal cortex. Rats were trained to respond to a brief light stimulus presented randomly in one of five spatial locations, with 100 trials per session. Once performance had stabilized rats were treated with escalating doses of amphetamine (three injections per week for 5 weeks at 1-5 mg/kg per week); testing was continued on nondrug days, and for several weeks of withdrawal. During the amphetamine-treatment and withdrawal phases accuracy of responding was unaffected, but errors of omission increased. Lengthening the stimulus duration abolished this effect. Reducing the stimulus duration also reduced response accuracy and this effect was more marked in amphetamine-treated rats. Both reduced accuracy, and increased omissions, seen in amphetamine-treated rats were reversed by injecting the D1 receptor agonist SKF38393 into the medial prefrontal cortex. This treatment also prevented the decline in accuracy in control animals that resulted from reducing the stimulus duration. These results, indicating that exposure to amphetamine induces a long-lasting deficit in visual attention, add to a growing list of deficits suggesting that amphetamine-sensitized state may model the cognitive deficit state in schizophrenia. The reversal of these deficits by a D1 receptor agonist provides further evidence that prefrontal D1 dopamine receptors are involved in cognition, and may be a potential target for treatment of impaired cognition in schizophrenia.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2005

Subgenual prefrontal cortex volumes in major depressive disorder and schizophrenia: diagnostic specificity and prognostic implications.

OBJECTIVE: A variety of findings have implicated the portion of the anterior cingulate cortex ventral to the corpus callosum in the pathophysiology of familial depressive disorder. There are, as yet, few data to address the specificity of these abnormalities to depressive disorders or to characterize their stability over time. METHOD: The authors studied 10 subjects who were judged to have had major depressive disorder with psychotic features, who underwent magnetic resonance imaging (MRI) protocols, and who participated in a longitudinal study of recent-onset psychosis. These were group-matched to 10 subjects with schizophrenia and to 10 well comparison subjects. Volumetric measures were made of the posterior and anterior portions of the subgenual prefrontal cortex for these 30 subjects. Follow-up scans done an average of 4 years after intake were available for seven subjects with major depressive disorder, nine subjects with schizophrenia, and five well comparison subjects. RESULTS: Volumes of the left side of the posterior subgenual prefrontal cortex differed significantly by group and were smallest for the group with psychotic major depressive disorder. Volumes of the anterior subgenual prefrontal cortex did not differ significantly by group. Patients with major depressive disorder were more likely to show increases in posterior subgenual prefrontal cortex volume on follow-up than were comparison subjects or patients with schizophrenia. CONCLUSIONS: These findings add to the evidence that abnormalities in the subgenual region of the anterior cingulate play a role in at least some types of mood disorder.

Adult↗
PubMed2003

Selective enhancement of functional connectivity in the left prefrontal cortex during sentence processing.

We present the results of correlation analyses for identifying temporally correlated activations between multiple regions of interest. We focused on functional connectivity for two regions in the prefrontal cortex: the left inferior frontal gyrus (L. F3t/F3O) and the left precentral sulcus (L. PrCS). Temporal correlations of functional magnetic resonance imaging signals were separately examined during a sentence comprehension task and a lexical decision task, thereby averaging data throughout all voxels within a region of interest used as a reference region. We found that the reciprocal connectivity between L. F3t/F3O and L. PrCS was significantly enhanced during sentence processing, but not during lexico-semantic processing, which was confirmed under both auditory and visual conditions. Furthermore, significantly correlated regions were mostly concentrated in the left prefrontal cortex during the sentence task. These results demonstrate that the functional connectivity within the left prefrontal cortex is selectively enhanced for processing sentences, which may subserve the use of syntactic information for integrating lexico-semantic information.

Adult↗
PubMed1991

Dopamine D1 autoreceptor function: possible expression in developing rat prefrontal cortex and striatum.

Synthesis-modulating dopamine (DA) autoreceptor function was studied in vivo using gamma-butyrolactone (GBL) to block propagation along DA axons. DA synthesis was measured by the accumulation of L-3,4-dihydroxyphenylalanine (L-DOPA) after inhibition of aromatic L-amino acid decarboxylase. GBL treatment markedly increased DOPA accumulation in both the striatum and prefrontal cortex of developing rats. The selective DA partial D1 agonist SKF-38393 inhibited this GBL-induced rise in DA synthesis in both the striatum and prefrontal cortex of 15- and 22-day-old rats, but not in adults. The effects of SKF-38393 in developing rats were mimicked by the non-catechol D1 partial agonist CY-208-243, and were blocked by the D1 antagonist SCH-23390, suggesting receptor mediation. The mixed D2/D3 agonist quinpirole attenuated DA synthesis in striatum of both two-week-old and adult rats, but failed to inhibit the GBL-induced increase in DA synthesis in the developing prefrontal cortex. These findings suggest that synthesis-modulating D1-like receptor function may emerge transiently in the developing mammalian forebrain. In the adult striatum these functions appear to be subsumed by D2-like receptors, whereas all synthesis-modulating DA receptor function in prefrontal cortex appears to be essentially lost with maturation.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1995

Increased dopamine and norepinephrine release in medial prefrontal cortex induced by acute and chronic stress: effects of diazepam.

We have examined the effects of diazepam on the stress-induced increase in extracellular dopamine and norepinephrine in the medial prefrontal cortex using in vivo microdialysis. In naive rats, acute tail pressure (30 min) elicited an increase in the concentrations of dopamine and norepinephrine in extracellular fluid of medial prefrontal cortex (+54 and +50%, respectively). Diazepam (2.5 mg/kg, i.p.) decreased the basal concentration of extracellular dopamine and norepinephrine. Diazepam also attenuated the stress-evoked increase in the absolute concentrations of extracellular dopamine (+17%), but did not alter the stress-induced increase in norepinephrine (+41%). However, when the drug-induced decrease in basal dopamine and norepinephrine concentration was taken into account, the stress-induced net increase in dopamine above the new baseline was equivalent to that obtained in vehicle pretreated rats, whereas the net increase in norepinephrine was almost twice that obtained in control subjects. In rats previously exposed to chronic cold (three to four weeks at 5 degrees C), tail pressure again produced an increase in the concentrations of dopamine and norepinephrine in the medial prefrontal cortex (+42% and +92%, respectively). However, in these chronically stressed rats, diazepam no longer decreased basal dopamine or norepinephrine in extracellular fluid, nor did it affect the stress-induced increase in the concentrations of these catecholamines. These data indicate that diazepam has complex effects on the extracellular concentrations of dopamine and norepinephrine which vary depending upon whether the rat is undisturbed or stressed during the period of drug exposure as well as the rat's prior history of exposure to stress. Moreover, these data raise questions regarding the role of catecholamines in the mechanism by which diazepam exerts its anxiolytic properties.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Language-activated cerebral blood oxygenation and hemodynamic changes of the left prefrontal cortex in poststroke aphasic patients: a near-infrared spectroscopy study.

BACKGROUND AND PURPOSE: In normal subjects, regional cerebral blood flow (rCBF) is greatly increased by neuronal activity, whereas the cerebral metabolic rate for O2 is increased only slightly. However, it is not clear what kinds of cerebral blood oxygenation and hemodynamic changes can be induced by language activities in language-relevant areas of poststroke aphasics. In the present study, we investigated the difference in the changes of cerebral blood oxygenation and hemodynamics in the left prefrontal cortex induced by language activities between normal subjects, poststroke nonaphasic patients, and nonfluent aphasic patients using near-infrared spectroscopy (NIRS). METHODS: Twenty-nine participants performed speech tasks, such as confrontational naming, to evaluate changes among poststroke nonfluent (Broca's) aphasia patients (10 cases; mean+/-SEM, 56.9+/-2.2 years), age-matched normal subjects (13 cases; 50.7+/-2.2 years) and poststroke nonaphasic patients (6 cases; 52.5+/-3.9 years). The optodes of NIRS were placed over the left prefrontal cortex. We analyzed the NIRS parameter (oxyhemoglobin [oxy-Hb], deoxyhemoglobin [deoxy-Hb], and total hemoglobin [total-Hb]) changes by qualitative pattern analysis of the parameter changes and quantitative analysis of the parameter values among the groups. RESULTS: The most common NIRS parameter change was an increase in oxy-Hb and total-Hb, with a slight decrease or no change in deoxy-Hb in the normal subjects (5 of 13 cases, 38.5%) and the nonaphasic cerebrovascular disease (CVD) patients (3 of 6 cases, 50.0%). In contrast, the most common pattern in the aphasic patients was an increase of deoxy-Hb, with an increase of oxy-Hb and total-Hb (5 of 10 cases, 50%). However, this pattern was observed in only 3 of 13 cases (23.1%) in the normal subjects and 1 of 6 cases (16.7%) in the nonaphasic CVD patients. The mean (+/-SEM) changes of deoxy-Hb of the aphasic patients, the normal subjects, and the nonaphasic CVD patients were 0.78+/-0.29, 0.06+/-0.16, and -0.18 +/- 0.22, respectively. The statistical analysis demonstrated a significant effect for deoxy-Hb (P<0.05), with the aphasic patients differing significantly from the normal subjects and the nonaphasic CVD patients, while the 2 nonaphasic groups did not differ from each other. CONCLUSIONS: The present results demonstrate a multiplicity of language-activated cerebral blood oxygenation and hemodynamic changes in the left prefrontal cortex in the nonaphasic and aphasic groups. The increase of deoxy-Hb with increases of oxy-Hb and total-Hb in the aphasics during language tasks suggests that the left prefrontal cortex of the aphasics utilizes more oxygen than the nonaphasics during language tasks. Finally, functional MRI, which images the activation area in the brain by detecting the reduced concentration of deoxy-Hb during neuronal activation, should be performed on the patients with cerebral dysfunction, giving special consideration to the possible multiplicity of the rCBF and cerebral oxygen metabolism responses to functional tasks.

Aged↗
PubMed2002

Specialization in the left prefrontal cortex for sentence comprehension.

Using functional magnetic resonance imaging (fMRI), we examined cortical activation under syntactic decision tasks and a short-term memory task for sentences, focusing on essential properties of syntactic processing. By comparing activation in these tasks with a short-term memory task for word lists, we found that two regions in the left prefrontal cortex showed selective activation for syntactic processing: the dorsal prefrontal cortex (DPFC) and the inferior frontal gyrus (IFG). Moreover, the left DPFC showed more prominent activation under the short-term memory task for sentences than that for word lists, which cannot be explained by general cognitive factors such as task difficulty and verbal short-term memory. These results support the proposal of specialized systems for sentence comprehension in the left prefrontal cortex.

Adolescent↗
PubMed2001

Alternate cadmium exposure differentially affects amino acid metabolism within the hypothalamus, median eminence, striatum and prefrontal cortex of male rats.

This work was designed to analyze the possible changes in glutamate, aspartate and glutamine content induced by cadmium exposure in the hypothalamus, striatum and prefrontal cortex of rats, using an alternate schedule of metal administration. Pubertal-adult differences were also evaluated. In adult control rats, glutamate and aspartate contents in the anterior hypothalamus decreased as compared to pubertal controls. After cadmium administration from day 30 to 60 of life, the content of anterior hypothalamic glutamate and aspartate diminished. In adult control animals, the glutamine content increased in mediobasal hypothalamus as compared to pubertal controls. After cadmium exposure from day 30 to 60 of life, the mediobasal glutamine content increased, and after cadmium treatment from day 60 to 90 of life, the mediobasal aspartate content decreased. In adult control rats the content of glutamine, glutamate and aspartate of the posterior hypothalamus decreased significantly. After cadmium administration in pubertal animals, posterior hypothalamic contents of glutamine, glutamate and aspartate diminished. Cadmium treatment of adult animals caused a decrease in glutamine content, as compared to controls. In adult control rats, only glutamate and aspartate content increased in the prefrontal cortex as compared to the values found in pubertal controls. When cadmium was administered to adult animals, only the aspartate content decreased. In the striatum, cadmium decreased the glutamine and aspartate contents when administered from day 60 to 90 of life. These data suggest that cadmium differentially affects amino acid metabolism in the hypothalamus, striatum and prefrontal cortex. Age-dependent effects of cadmium on these brain areas appeared to have occurred.

Aging↗
PubMed1990

Metabolic effects obtained from excitatory amino acid stimulation of the sulcal prefrontal cortex.

Indirect calorimetry was used to assess metabolic changes in rats following injections of the excitatory amino acid D,L-homocysteic acid (DLH) into the sulcal or medial prefrontal cortex. Injection of 7 nmol of DLH into the sulcal prefrontal cortex (SPC) increased respiratory quotient (RQ), indicating increased utilization of carbohydrate as an energy substrate. This treatment also decreased energy expenditure in the absence of related changes in motor activity, suggesting an inhibition of thermogenesis. A larger dose of DLH (50 nmol) injected into the SPC caused opposite effects, with a significant decrease in RQ and increased energy expenditure and motor activity. Rectal temperature was also increased by 20 or 50 nmol DLH but decreased with 7 nmol DLH. The anatomical specificity of these effects was indicated in that equivalent injections DLH into the medial prefrontal cortex did not affect energy balance. From this and related evidence it is concluded that SPC neurons exert a potent influence upon thermogenesis and metabolic substrate utilization that is bidirectional according to the magnitude of the excitatory stimulation that is applied.

Analysis of Variance↗
PubMed1992

Cocaine facilitation of prefrontal cortex self-stimulation: a microstructural and pharmacological analysis.

A novel self-stimulation methodology involving a fixed-interval (FI-5 s) schedule of reinforcement, microanalysis and threshold evaluation was used to investigate the effects of cocaine on rats lever pressing for electrical stimulation of the prefrontal cortex. Cocaine (15 mg/kg) increased medial prefrontal cortex (MPC) self-stimulation rates under FI-5 by a mean of 269% and reduced current thresholds for self-stimulation. A similar facilitation was evident with self-stimulation of the sulcal prefrontal cortex. Microanalysis showed that cocaine decreased inter-response times and post-reinforcement pauses, increased responding in the second and third quartiles of the inter-reinforcement interval (IRI) and decreased responding in the fourth IRI quartile. Schedule control of responding was still evident following cocaine despite the profound facilitation of response rates. Increased response rates were seen up to 48 h following a single dose of cocaine, suggesting sensitization of the PFC reinforcement substrate. The acute effects of cocaine on MPC self-stimulation were completely reversed by the dopamine (DA) D1 antagonist SCH 23390 0.02 mg/kg) and the D2 antagonist raclopride (0.3 mg/kg) but not by naloxone (0.5 mg/kg). These results are consistent with previous studies demonstrating the PFC as part of the neural substrate mediating cocaine reward. Further, these results implicate DA receptors in the reinforcing properties of both cocaine and MPC self-stimulation.

Animals↗