Biomedical subjects

B J Hoffer

Publications and source records attributed to B J Hoffer.

At least 91 records · Page 5Linked to original sources

PubMed1992

Eighteen-month course of two patients with grafts of fetal dopamine neurons for severe Parkinson's disease.

Two patients with advanced Parkinson's disease were followed for 6 months before, and 18 months after, receiving stereotaxic grafts of fetal mesencephalic tissue from aborted human fetuses. Parameters studied included a series of standardized tests of movement, response to levodopa, electrophysiological recording of the motor readiness potential, and positron emission tomography (PET) with ligands based upon levodopa and upon the dopamine reuptake inhibitor nomifensine. The patients each received stereotaxic implantation of ventral mesencephalic tissue containing midbrain dopamine neurons from aborted human fetuses of 8 to 10 weeks gestational age into the caudate and putamen of one hemisphere. Throughout their 18-month course, the patients were treated with cyclosporine, azathioprine, and glucocorticoids to minimize the risk of graft rejection. There were no significant complications from the procedure, but there was also no major change in their assessment of impairment on the Hoehn and Yahr scale. However, significant changes were observed in clinical, electrophysiological, and PET measures. Changes in these parameters, apparent at 6 months postoperatively, were described in detail in a previous report. The purpose of this present report is to provide follow-up data from the subsequent year with an emphasis on longitudinal evaluation methodology. Standardized clinical testing showed a small but long-term improvement in the first of the two patients. Following the operation, she was able to walk in "off" periods, which she had not been able to do preoperatively. This improvement was accompanied by increased walking speed and reduction in the time necessary to perform a series of pronation and supination movements using both hands. Although these improvements have continued throughout the postoperative period, they have not alleviated her basic neurological impairment. The second patient showed similar improvement during the first 6 months; she then reverted to her preoperative status at the end of the 18-month follow-up period. The electrophysiological recordings were consistent with the clinical findings. Both patients had significant changes in the motor readiness (bereitschafts) potential amplitude, which was greatest 5 to 7 months postoperation. The amplitude of the potential declined subsequently for both patients, but remained significantly elevated over the preoperative baseline for patient 1. The analysis of the PET scans was somewhat compromised by technical problems in the preoperative scans. However, they are also consistent with the clinical data. In comparisons of the operated and the unoperated sides, fluoro-dopa showed increased uptake in the caudate nucleus of patient 1 at 6 months and at 13 months.(ABSTRACT TRUNCATED AT 400 WORDS)

Brain Tissue Transplantation↗

PubMed1992

Comparison of fetal rabbit brain xenografts to three different strains of athymic nude rats: electrophysiological and immunohistochemical studies of intraocular grafts.

Interest in the use of neural tissue transplantation for the study of CNS development and maturation and the potential use of this technique for the treatment of certain degenerative CNS disorders has led to our use of transplantation of neural tissue across species lines. Prior to extensive transplantation studies using athymic rats as recipients, we wished to evaluate the currently available strains of athymic rat for their suitability as host animals for xenografts of neural tissue. Fetal cerebellar and cerebral cortex tissue from rabbit brain of gestational age 20-25 days was dissected and transplanted to the anterior chamber of the eye of Harlan Wisconsin, Fisher 344 Jnu, or NCI-Harlan athymic nude rat strains. The brain tissue grafts were allowed to mature for 3 mo during which time the size and vascularity of each graft was monitored through the cornea of anesthetized hosts. In each group all of the transplants survived and grew to varying extents in the anterior chamber of the eye. Following the growth study in vivo extracellular recording of single neuronal activity was performed. Spontaneous neural activity was found in most transplants in all three groups with no difference in the viability or discharge rates of neurons between the groups. Illumination of the ipsilateral eye increased the firing rate of neurons in all three groups, suggesting excitatory cholinergic innervation of the grafted neurons from the host parasympathetic iris ground plexus. Antibodies directed against neurofilament protein, glial fibrillary acidic protein, synapsin, and tyrosine hydroxylase were used to characterize the transplants immunocytochemically and revealed no differences between the grafts in the three groups of recipients. All transplants contained significant numbers of glial and neuronal elements with the distribution resembling that in adult brain tissue. Some of the transplants contained a sparse innervation of tyrosine hydroxylase-positive fibers from the sympathetic plexus of the host iris. Furthermore, synapsin-immunoreactivity suggested that synaptogenesis had taken place within the grafts. Histological examination of the grafts revealed that 67% of the grafts had been infiltrated, to varying extents, by lymphocytes which led to areas of cell lysis and necrosis. All host animals had populations of T-cell receptor positive cells, most of which also expressed the T-cell surface antigens CD4 and CD8. However, no transplants were overtly rejected over the 15 wk period of study.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1992

Clearance and diffusion of locally applied dopamine in normal and 6-hydroxydopamine-lesioned rat striatum.

Studies of dopamine (DA) clearance and diffusion were carried out after unilateral destruction of striatal DA afferents using intraparenchymal injection of 6-hydroxydopamine (6-OHDA). Rats were screened for the extent of DA depletion by testing for contralateral rotations induced by 0.05 mg/kg of apomorphine. Exogenous DA clearance and diffusion were determined using rapid (5 Hz) in vivo chronoamperometry with Nafion-coated carbon-fiber electrodes. Local applications of DA by pressure ejection from micropipettes into the lesioned vs. nonlesioned striata, with dose adjusted to elicit roughly equivalent amplitudes of electroactive signals, manifested a much prolonged clearance time on the lesioned side. A second protocol involved administration of equal volumes (amounts) of DA into lesioned vs. nonlesioned striata. In such cases, a volume of DA which manifested no detectable signal on the intact side produced a pronounced electrochemical signal on the lesioned side. When nomifensine, a high-affinity DA uptake inhibitor, was locally applied into the intact striatum, a subsequent ejection of DA produced a much larger signal than when the same volume was given before nomifensine. Very little or no effects of nomifensine were seen in 6-OHDA-lesioned striata. Taken together, these data indicate a much prolonged clearance time of DA in 6-OHDA-denervated striata. Moreover, the data also suggest that the primary mechanism underlying this effect is the loss of high affinity neuronal uptake. Thus, such changes in DA clearance may help account for some of the well documented compensatory phenomena which occur after DA-depleting lesions in animals and in man.

Animals↗

PubMed1991

Norepinephrine and isoproterenol increase the phosphorylation of synapsin I and synapsin II in dentate slices of young but not aged Fisher 344 rats.

A number of recent reports have suggested that norepinephrine (NE) produces a form of synaptic enhancement that resembles long-term potentiation (LTP). LTP, thought to be an electrophysiological correlate of memory, in part involves an augmentation of transmitter release. Although the effects of NE have not been unequivocally linked to LTP, it is clear that NE can produce increased transmitter release in the dentate gyrus of the hippocampus. The purpose of this study was to determine whether NE was capable of enhancing the phosphorylation of synapsin I and synapsin II, two homologous phosphoproteins thought to be involved in modulation of neurotransmitter release. NE (10 microM) and isoproterenol (250 nM) produced an increase in the phosphorylation of synapsin I and synapsin II in dentate slices from young rats. Phosphorylation site analysis of synapsin I, performed by limited proteolysis, indicated that NE and isoproterenol increased the phosphorylation of synapsin I at sites modified by Ca2+/calmodulin-dependent protein kinase II as well as cAMP-dependent protein kinase. These data demonstrate that NE stimulates the phosphorylation of synapsin I at its Ca2+/calmodulin-dependent protein kinase II site, which is a site that has been shown to regulate the effect of synapsin I on neurotransmitter release. We have also examined the effects of NE and isoproterenol on synapsin phosphorylation in dentate slices prepared from aged animals. Such animals have previously been shown to exhibit deficits in NE sensitivity as well as significant impairment in their ability to exhibit LTP. Neither NE nor isoproterenol stimulated synapsin phosphorylation in slices prepared from aged animals. Interestingly, the basal level of phosphorylation of the synapsin proteins was higher in slices prepared from aged animals. This higher basal level of phosphorylation may underlie the failure of aged animals to exhibit NE-stimulated increases in phosphorylation of the synapsin proteins. We hypothesize that the beta-adrenergic agonist-stimulated phosphorylation of synapsin I and synapsin II in young rats plays a role in the increase in transmitter release produced by NE in the dentate. Thus, the failure of the aged rats to show such phosphorylation may underlie, in part, their failure to exhibit normal responsiveness to NE. Moreover, these deficits in synapsin phosphorylation may also play some role in the deficits in plasticity seen in aged rats.

Aging↗

PubMed1991

Functional innervation of spinal cord tissue by fetal neocortical grafts in oculo: an electrophysiological study.

The ability of fetal neocortex transplants, to functionally innervate maturated cervical spinal cord grafts in oculo, was investigated in rats. We found that a neocortex co-graft will grow and develop in contact with a spinal cord graft, and will generate a functional input to maturated spinal cord tissue which can be activated by electrical stimulation of the neocortex graft. Our data suggest that orthodromic stimulation of this pathway causes short latency, transient excitations of spinal graft neurons. These appear to be mediated by an excitatory amino acid receptor since the response was noncompetitively antagonized by kynurenic acid. Kynurenic acid also noncompetitively antagonized the excitatory effects of glutamate superfused over single spinal cord grafts. The mechanism of the excitation probably does not involve an NMDA (N-methyl-D-aspartate) receptor since APV (2-amino-5-phosphonovalerate) did not alter the spinal graft neuronal responses to neocortical co-graft stimulation. These data suggest that fetal neocortex can functionally innervate maturated cervical spinal cord in the in oculo graft preparation. The in oculo spinal cord graft model may thus provide a unique test system for studies of the influence of drugs and other manipulations that might alter cortico-spinal pathway development as well as influence reestablishment of neuronal pathways after spinal cord injury.

Action Potentials↗

PubMed1991

Acidic and basic fibroblast growth factors augment growth of fetal brain tissue grafts.

The fibroblast growth factor family of peptides (FGF's) are biological regulators which have a diverse array of activities. Among the biological responses reported are inductive effects during early embryogenesis, mitogenic activity on a variety of mesenchymally derived tissues, potent angiogenic activity and neurotrophic activity for both the peripheral and central nervous system. In vitro studies have been performed showing that the FGF's play a regulatory role in the survival and growth of neurons from several regions of the developing rat brain. By using the in vivo model of intraocular transplantation and repeated injections into the anterior chamber, we have been able to observe and follow the survival and growth of small, defined areas of central nervous system (CNS) under the influence of acidic (a) FGF or basic (b) FGF. Acidic FGF significantly enhanced growth of transplanted parietal cortex, embryonic day 17-20 [E17-20], hippocampus [E20] but not spinal cord [E14] when compared to the bovine serum albumin (BSA) vehicle alone. Parietal cortex grafts increased approximately 200% and the hippocampus grafts 100% when stimulated with aFGF. Basic FGF greatly enhanced the growth of intraocularly transplanted parietal cortex (E17-18), hippocampus (E16-17), and spinal cord (E14) by approximately 400%, 100% and 50% respectively when compared to the vehicle alone, and was thus significantly more potent than aFGF at the same concentration. Effects on all areas were seen using concentrations of aFGF down to 25 micrograms/ml and bFGF as low as 2.5 micrograms/ml. Histochemical and immunohistochemical studies carried out on cryostat sectioned grafts suggested either no change or normalization of markers for vascularization, glial and neuronal populations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Ethical issues in brain-cell transplantation.

The ethical ramifications of intracranial transplantation are many. While the majority of ethical concerns have focused on the relationship of transplantation of fetal brain tissue to elective abortion, there are other significant issues relating to graft recipients (patients and their families) and to the allocation of public resources for clinical transplantation research. In this article, some of these latter problems will be considered first, followed by a discussion of the constraints derived from the abortion question that are placed on transplantation.

Aborted Fetus↗

PubMed1990

Multichannel semiconductor-based electrodes for in vivo electrochemical and electrophysiological studies in rat CNS.

Five-channel silicon-based microprobes were sputter-coated with carbon, coated with Nafion, and used for both in vivo electrochemical and single-unit electrophysiological recordings. High-speed electrochemical studies were performed in vitro and in vivo, which demonstrated that these multisite probes were capable of monitoring the evoked overflow of monoamines in selected brain regions of the rat. In addition, action potentials from Purkinje cells in the rat cerebellum, identified electrophysiologically, were recorded from different sites on the same probe. Spontaneous firing rates could be monitored for up to 2 hours in order to investigate the effects of systemic administration of phencyclidine. These results provide preliminary evidence that solid-state multi-site probes can be utilized for both in vivo electrochemical and electrophysiological studies in the rat brain.

Animals↗

PubMed1990

GABAergic mechanisms in the electrophysiological actions of ethanol on cerebellar neurons.

We have found that the partial inverse benzodiazepine agonists Ro 15-4513 and FG 7142 antagonize the depressant electrophysiological effects of locally applied ethanol in the cerebellum. Although absolute tissue concentrations are not known, dose-response curves constructed using pressure-ejection doses as previously described we found that FG 7142 was more efficacious, but less potent than Ro 15-4513. Our observation that ethanol and inverse benzodiazepine agonists have interactions which are not competitive might suggest that these two drugs act through separate, but interactive mechanisms in order to produce the observed ethanol antagonism. If such independent interactions were mediated at different sites on a given macromolecular complex, such as the GABAa/Cl- channel, then one might expect to find allosteric interactions between those sites as well as with the functional response of the complex to GABA activation. Indeed, this hypothesis is consistent with the recent finding of Harris and collaborators that ethanol potentiates the inverse agonist actions of Ro 15-4513 and FG 7142. On the other hand, we were unable to find large ethanol-induced potentiations of GABA effects on all neurons which showed depressant responses to ethanol administration in rat cerebellum. However we did find that the GABAa antagonist, bicuculline, blocks the depressant effects of ethanol on the same neurons. We conclude that the interaction between ethanol and GABA probably does not occur directly at the GABAa receptor site, but that the GABAa mechanism does play a permissive role in the ethanol-induced depressions of cerebellar Purkinje neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed1990

Truncated IGF-1 exerts trophic effects on fetal brain tissue grafts.

Truncated IGF-1 (tIGF-1), a form of IGF-1 identified in the human brain, has been suggested, from in vitro experiments, to exert neurotrophic effects on developing fetal brain tissue. We studied the effects of tIGF-1 and IGF-1 on small defined areas of the developing central nervous system by using the in vivo model of intraocular transplantation which allows for direct observations of graft survival and growth. Truncated IGF-1 was found to significantly enhance the growth of fetal spinal cord (Embryonic Day (E) 14) and parietal cortex (E16-17) grafts transplanted to the anterior chamber of the eye of adult rats. tIGF-1 increased the volume of cerebral cortex grafts by approximately 100% and of E14 spinal cord grafts by approximately 50%. E18 spinal cord grafts and hippocampal grafts were not stimulated by tIGF-1 as compared to controls given HSA. Effects in cortex were seen with tIGF-1 using concentrations down to at least 10 ng/microliters. Interestingly, intact IGF-1 had no effect on cortical grafts. These findings show for the first time, using an in vivo system, that tIGF-1 is a potent stimulator of growth of grafted fetal cortex cerebri and spinal cord and suggest a possible role for endogenous tIGF-1 in cortical and spinal cord development.

Animals↗

PubMed1990

Potentiation of gamma-aminobutyric acid-mediated inhibition by isoproterenol in the cerebellar cortex: receptor specificity.

A large body of electrophysiological data has supported the hypothesis that an important role of norepinephrine in the central nervous system is to modulate the actions of other transmitter systems, particularly those utilizing the amino acid neurotransmitters. Noradrenergic potentiation of inhibitory responses, induced by locally-applied or synaptically-released gamma-aminobutyric acid (GABA) on cerebellar Purkinje neurons, has been observed by a number of investigators, who have suggested that activation of beta-adrenergic receptors plays a critical role in mediating this modulatory effect of norepinephrine (NE). Two postsynaptic receptors for GABA, termed A and B, have been identified and both subtypes have been found in the cerebellum of the rat. The purposes of this investigation were first to identify the subtype(s) of GABA receptor responsible for mediating the inhibitory effects of locally-applied GABA in the cerebellar cortex and second to identify which subtype of GABA receptor is modulated by a beta-adrenergic input. Inhibitory responses of cerebellar Purkinje neurons, in urethane-anesthetized rats, to iontophoretic or pressure-applied isoguvacine, a selective GABAA agonist, to baclofen, a GABAB agonist or to GABA itself, were examined before, during and after local application of isoproterenol or norepinephrine. Isoguvacine, but not baclofen, induced consistent and dose-dependent inhibition of the firing of Purkinje cells. At ejection currents that had no effect on spontaneous firing rate, iontophoretically-applied isoproterenol potentiated isoguvacine-induced inhibition. These data suggest that GABAA, rather than GABAB receptors, mediate GABA-induced inhibitions of cerebellar Purkinje neurons. Moreover, it appears that the modulation of GABA function by beta adrenergic agonists involves an interaction between a beta-adrenergic input and the GABAA receptor complex.

Action Potentials↗

PubMed1990

Toxic effects of lead on neuronal development and function.

The effects of lead on the development of the nervous system are of immediate concern to human health. While it is clear that lead can affect neuronal development at levels of exposure within the range found in the environment, the particular mechanism of the disruption is not readily ascertained. Lack of knowledge of the mechanisms of lead-induced damaged hampers its treatment and prevention. The goal of our research is to develop a model system in which the effects of lead on central nervous system development can be demonstrated. The complexity of the brain hampers such investigations because often it is not clear if apparent toxic effects represents changes secondary to somatic changes, such as endocrine or hematological defects, that could alter brain development, or even transneuronal effects caused by toxicity at a distal site that deprives a brain area of a synaptic input needed for its proper development. A related problem is the redundancy of compensatory systems in the brain. Such system may disguise the severity of the initial toxic insult and themselves can cause functional disturbances. To study neuronal development in a system that minimizes such difficulties, we have grafted discrete brain regions derived from rat fetuses into the anterior chamber of the eye of adult hosts. The brain pieces continue organotypic development of the eye, but are isolated from possible secondary changes due to alterations in the development of the endocrine and other somatic systems because the adult host has these systems already fully developed. Similarly, effects mediated by connecting brain areas are minimized since the transplant is isolated in the anterior chamber of the eye.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic Fibers↗

PubMed1990

Electrophysiologic effects of ethanol in human brain xenografts in oculo: antagonism by Ro15-4513.

Human cortex cerebri and cerebelli xenografts from first-trimester fetal tissue fragments were used to study the effects of ethanol on single human central neurons. Transplants were placed into the anterior eye chamber of athymic nude rats and allowed to develop for 3 to 11 months. Immunohistologic analysis revealed graft structures that stained positively for a number of neuronal, transmitter-related, glial and vascular markers. Superfusion of ethanol (EtOH) elicited a reversible and dose-dependent depression of action potential discharge. At least two populations of neurons could be identified--a more sensitive group with an EC50 of 3.0 mM and a less sensitive group with an EC50 of 22.4 mM. These EtOH levels are within the range eliciting behavioral signs of intoxication in humans. EtOH-induced depressions could be antagonized by administration of the benzodiazepine inverse agonist Ro 15-4513. This study represents the first demonstration, to our knowledge, of the electrophysiologic actions of EtOH on single neurons from human brain, and provides dose-response data collected with known concentrations of EtOH as well as evidence for the blockade of these EtOH effects by the Roche compound.

Animals↗

PubMed1989

The effects of cholecystokinin (CCK-8) on dopamine-containing nerve terminals in the caudate nucleus and nucleus accumbens of the anesthetized rat: an in vivo electrochemical study.

The action of cholecystokinin (CCK) on presynaptic function of dopaminergic nerve terminals has been the subject of much debate in the literature. In efforts to resolve some of the reported ambiguities, high speed in vivo electrochemical recordings were carried out in the caudate nucleus and nucleus accumbens of the urethane anesthetized rat, to determine effects of locally applied sulfated (CCK-8S) and unsulfated (CCK-8US) CCK octapeptide. Locally-applied CCK-8S and CCK-8US caused no increase in the baseline electrochemical signals recorded from either brain region. However, locally applied CCK-8S potentiated the potassium-evoked overflow of dopamine (DA) into the extracellular space in both the caudate and nucleus accumbens. In contrast, pressure ejection of CCK-8US produced no significant effects on the potassium-evoked overflow of DA in either structure. These data support a facilitatory effect of CCK-8S on potassium-evoked overflow from DA-containing nerve terminals in the urethane anesthetized rat that is likely mediated through a peripheral type CCK receptor.

Anesthesia↗

PubMed1989

Kappa-bungarotoxin blockade of nicotine electrophysiological actions in cerebellar Purkinje neurons.

The agonistic actions of nicotine in cerebellum were selectively blocked by kappa-bungarotoxin depending on the cell type studied. Nicotine-induced Purkinje cell inhibitions were antagonized by the simultaneous application of this toxin. In contrast, nicotine-induced cerebellar interneuron excitations were unaltered. These findings suggest that kappa-bungarotoxin may be used as a selective pharmacological tool for the study of nicotine actions which are dependent on ganglionic-like receptors, which have been associated with Purkinje cells in previous studies.

Action Potentials↗

PubMed1989

Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson's disease. A detailed account of methodology and a 6-month follow-up.

By using stereotaxic surgical techniques, ventral mesencephalic tissues from aborted human fetuses of 8 to 10 weeks' gestational age were implanted unilaterally into the striata in two patients with advanced Parkinson's disease. The patients were treated with a cyclosporine, azathioprine, and steroid regimen to minimize the risk for graft rejection. They were examined for 6 months preoperatively and 6 months postoperatively and continued to receive the same doses of antiparkinsonian medication. There were no significant postoperative complications. No major therapeutic effect from the operation was observed. However, in the clinical tests, both patients showed small but significant increases of movement speed for repeated pronation-supination, fist clenching, and foot lifting. The rate of walking also increased in the one patient tested. For both patients, there was an initial worsening postoperatively, followed by improvement vs preoperative performance at 1 to 3 months. Both patients also showed significant improvement in the magnitude of response to a single dose of levodopa (L-dopa), but there was no increase in the duration of drug action. The motor readiness potential increased in both patients postoperatively, primarily over the operated hemisphere. Neurophysiological measurements also showed a more rapid performance of simple and complex arm and hand movements on the side contralateral to transplantation in one patient at 5 months postoperatively. Positron emission tomography demonstrated no increased uptake of 6-L-(18F)-fluorodopa in the transplanted striatum at 5 and 6 months. Taken together, these results suggest that the fetal nigral implants may have provided a modest improvement in motor function, consistent with the presence of small surviving grafts. Although our results support further scientific experimentation with transplantation in Parkinson's disease, widespread clinical trials with this procedure are probably not warranted at this time.

Contingent Negative Variation↗

PubMed1989

Human ventral mesencephalic xenografts to the catecholamine-depleted striata of athymic rats: ultrastructure and immunocytochemistry.

On the basis of animal studies, grafts of fetal human dopaminergic cells have been suggested as a therapy for Parkinson's disease. The purpose of this study was to characterize the ultrastructure and immunocytochemistry of human ventral mesencephalic xenografts placed into the catecholamine-depleted striata of athymic "nude" rats. Human fetal tissue was obtained from tissue fragments derived from elective abortions during the first trimester of pregnancy. Small pieces of the basal mesencephalon were grafted into the catecholamine-depleted striata of four athymic nude rats. The rats were allowed to survive from 3 to 6 months after grafting; following fixation, the striatal tissue containing the grafts was labeled with antibodies against tyrosine hydroxylase and serotonin. Immunocytochemistry revealed tyrosine-hydroxylase-like-immunoreactive (THLI) and serotoninlike-immunoreactive (5HTLI) cell bodies within the human grafts. Both 5HTLI and THLI fibers crossed the graft-host interface and innervated the previously lesioned striatum. Both types of fibers also entered the host cortex from the adjacent human graft. At the ultrastructural level, THLI and 5HTLI fibers and synaptic terminals were observed in the host neuropil. THLI and 5HTLI dendrites and axon terminals were also observed in the neuropil of the grafts themselves. THLI axon terminals are not normally present in the substantia nigra. The results of our study indicate that human xenografts can survive in the neuropil of the host striatum and form morphologically appropriate synapses within the host brain.

Animals↗

PubMed1989

In vivo electrochemical studies of monoamine release in the medial prefrontal cortex of the rat.

The magnitude and duration of release of monoamines evoked by local applications of potassium were measured in vivo in the medial prefrontal cortex using high-speed chronoamperometry. Typical electrochemical signals reflecting released of electroactive species ranging from 0.5 to 3.0 microM and lasting 90-120 s were detected at a variety of dorsal-ventral and anterior-posterior electrode placements in the medial prefrontal cortex. The magnitude of the reduction current measured following the oxidation reaction suggests a contribution of both serotonin and dopamine to the electrochemical signal, dopamine serving as the predominant monoamine in the medial prefrontal cortex proper and serotonin appearing to predominant in the more posterior regions of the frontal cortex. This conclusion was reinforced by the fact that unilateral 6-hydroxydopamine lesions of ascending dopamine fibers almost completely abolished electrochemical signals in the ipsilateral but not in the contralateral medial prefrontal cortex. The present study provides an in vivo characterization of monoamine release in the mesocortical dopamine terminal field, where it has been suggested that psychomotor stimulants may produce some of their positive reinforcing effects.

Dopamine↗