Biomedical subjects

G A Gerhardt

Publications and source records attributed to G A Gerhardt.

At least 37 records · Page 2Linked to original sources

PubMed1999

An automated movement assessment panel for upper limb motor functions in rhesus monkeys and humans.

As part of our studies of age-associated changes in motor functions, we have designed an automated movement assessment panel (MAP) to evaluate upper limb and hand movements. Here we describe two versions of the MAP, one for human testing and one for nonhuman primates, and methods for conducting parallel tests in rhesus monkeys and human volunteers. The results are reported from a battery of tests on young adult rhesus monkeys (n = 10, 5-8 years old), young adult human subjects (n = 10, 18-22 years old) and ten aged human subjects (n = 10, 66-68 years old) to demonstrate the capability of the MAP in quantifying arm and hand movement times. The performance times on the two simplest tasks tested were consistent from trial to trial, demonstrating that a stable behavioral baseline could be established for evaluating changes in motor functions over time and assessing treatments for improving motor functions. Motor learning was seen in the more complex movement tasks tested, indicating their usefulness in analyzing this behavior. Finally, age-associated changes in performance times were robustly delineated by the four tasks evaluated in the human subjects.

Adolescent↗

PubMed1999

Multiple single-unit recordings in the striatum of freely moving animals: effects of apomorphine and D-amphetamine in normal and unilateral 6-hydroxydopamine-lesioned rats.

Ensembles of striatal neurons were recorded in freely moving normal and unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats using chronically implanted electrode arrays. Animals received bilateral striatal implants of two 16-microwire arrays 1 week before recordings. Identified striatal neurons were categorized as medium spiny-like and large aspiny-like based on a combination of their activity autocorrelations and firing rates. Baseline firing rates of medium spiny-like neurons in the 6-OHDA-lesioned striata were significantly faster than were firing rates of the same neurons in the intact hemispheres of 6-OHDA-lesioned rats or normal animals. However, firing rates of large aspiny-like neurons were faster in both hemispheres of the 6-OHDA-lesioned rats as compared to normal animals. Interestingly, firing rates of neurons in all groups decreased by fivefold or greater under urethane anesthesia, although the relative firing rates between hemispheres were unchanged. d-Amphetamine (5.0 mg/kg, s.c.) increased the firing rates of both types of striatal neurons by twofold or greater in normal rats and in the intact hemispheres of 6-OHDA-lesioned animals. By contrast, this treatment did not alter neuron firing in the 6-OHDA-lesioned striata. Apomorphine (0.05 mg/kg, s.c.) did not affect neuronal firing rates either in normal rat striatum or in the unlesioned hemispheres of 6-OHDA-lesioned animals. However, it did significantly increase the firing rate of the medium spiny-like neurons in 6-OHDA-lesioned striata. These results demonstrate that the dopaminergic innervation of the striatum differentially influences two electrophysiologically distinct sets of striatal neurons in freely moving rats.

Anesthesia↗

PubMed1999

5-HT1B antagonists modulate clearance of extracellular serotonin in rat hippocampus.

In vivo chronoamperometry was used to determine the effects of locally applied antagonists of the serotonin-1B (5-HT1B) receptor (cyanopindolol, 5-HT-moduline and methiothepin) on the clearance of 5-HT in the CA3 region of the dorsal hippocampus and the corpus callosum (a brain region devoid of serotonin transporters and 5-HT1B receptors) of the rat. When 5-HT was pressure ejected into these regions, reproducible signals were detected. In the CA3 region, local application of 5-HT1B antagonists decreased the rate of clearance of the serotonin signal comparably to the selective 5-HT uptake inhibitor (SSRI), fluvoxamine. By contrast, in the corpus callosum, none of the drugs altered the 5-HT signal. One interpretation of these data is that 5-HT1B receptors can modulate the activity of the 5-HT transporter.

Analysis of Variance↗

PubMed1999

Multiple single units and population responses during inhibitory gating of hippocampal auditory response in freely-moving rats.

Paired clicks were presented to awake, freely-moving rats to examine neuronal activity associated with inhibitory gating of responses to repeated auditory stimuli. The rats had bundles of eight microwires implanted into each of four different brain areas: CA3 region of the hippocampus, medial septal nucleus, brainstem reticular nucleus, and the auditory cortex. Single-unit recordings from each wire were made while the local auditory-evoked potential was also recorded. The response to a conditioning stimulus was compared to the response to a test stimulus delivered 500 ms later: the ratio of the test response to the conditioning response provided a measure of inhibitory gating. Auditory-evoked potentials were recorded at all sites. Overall, brainstem reticular nucleus neurons showed the greatest gating of local auditory-evoked potentials, while the auditory cortex showed the least. However, except for the auditory cortex, both gating and non-gating of the evoked response were recorded at various times in all brain regions. Gating of the hippocampal response was significantly correlated with gating in the medial septal nucleus and brainstem reticular nucleus, but not the auditory cortex. Single-unit neuron firing in response to the clicks was most pronounced in the brainstem reticular nucleus and the medial septal nucleus, while relatively few neurons responded in the CA3 region of the hippocampus and the auditory cortex. Taken together, these data support the hypothesis that inhibitory gating of the auditory-evoked response originates in the non-lemniscal pathway and not in cortical areas of the rat brain.

Animals↗

PubMed1999

Methodology for coupling local application of dopamine and other chemicals with rapid in vivo electrochemical recordings in freely-moving rats.

Methodology is presented for constructing and using an electrode/microcannulae assembly that allows in vivo electrochemical measurements coupled with local application of dopamine (DA) and other chemicals in the unanesthetized freely-moving rat. Rats were implanted with a voltammetric electrode constructed of a carbon fiber sealed in fused silica tubing attached to a pair of stainless steel guide cannulae, into which fused silica injection cannulae were inserted for local application of DA and other chemicals. Precise delivery of nanoliter volumes was accomplished using a syringe drive combined with a fluid swivel to deliver the solutions to the injection cannulae. A newly-designed miniature potentiostat connected to a commutator via a modular telephone jack assembly allowed for high-speed chronoamperometric electrochemical recordings in freely-moving rats. Initial experiments characterized the in vitro electrochemical recording characteristics of the voltammetric electrode. In vivo studies were also carried out to study clearance of locally-applied DA and of potassium-evoked endogenous DA in the striatum and nucleus accumbens of freely-moving rats. In addition, the effects of chloral hydrate anesthesia on DA clearance signals in the nucleus accumbens were investigated. Moreover, the stability and reproducibility of this recording technique for measuring exogenous DA clearance was verified over a period of 5 days. Finally, the concurrent effects of systemic cocaine injection on DA uptake in nucleus accumbens and locomotor activity were examined. These studies support the conclusion that the methodology described herein allows for rapid chronoamperometric electrochemical recordings in freely-moving rats with precise microapplications of DA and other chemicals combined with concurrent measures of animal behavior.

Anesthesia↗

PubMed1999

GDNF improves dopamine function in the substantia nigra but not the putamen of unilateral MPTP-lesioned rhesus monkeys.

Microdialysis measurements of dopamine (DA) and DA metabolites were carried out in the putamen and substantia nigra of unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned rhesus monkeys that received intraventricular injections of vehicle or glial-derived neurotrophic factor (GDNF, 300 microg) 3 weeks prior to the microdialysis studies. Following behavioral measures in the MPTP-lesioned monkeys, they were anesthetized with isoflurane and placed in a stereotaxic apparatus. Magnetic resonance imaging (MRI)-guided sterile stereotaxic procedures were used for implantations of the microdialysis probes. Basal extracellular levels of DA and the DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were found to be decreased by >95% in the right putamen of the MPTP-lesioned monkeys as compared to normal animals. In contrast, basal DA levels were not significantly decreased, and DOPAC and HVA levels were decreased by only 65% and 30%, respectively, in the MPTP-lesioned substantia nigra. Significant reductions in d-amphetamine-evoked DA release were also observed in the MPTP-lesioned substantia nigra and putamen of the monkeys as compared to normal animals. A single intraventricular administration of GDNF into one group of MPTP-lesioned monkeys elicited improvements in the parkinsonian symptoms in these animals at 2-3 weeks post-administration. In addition, d-amphetamine-evoked overflow of DA was significantly increased in the substantia nigra but not the putamen of MPTP-lesioned monkeys that had received GDNF. Moreover, post-mortem brain tissue studies showed increases in whole tissue levels of DA and DA metabolite levels primarily within the substantia nigra in MPTP-lesioned monkeys that had received GDNF. Taken together, these data support that single ventricular infusions of GDNF produce improvements in motoric behavior in MPTP-lesioned monkeys that correlate with increases in DA neuronal function that are localized to the substantia nigra and not the putamen.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1999

Voltage-dependency of the dopamine transporter in the rat substantia nigra.

The possible voltage-dependence of the dopamine transporter (DAT) was investigated using electrophysiological and electrochemical recordings in rat brain slices containing the substantia nigra (SN). Whole-cell patch clamp recordings of DA neurons, revealed that addition of 15 mM KCl rapidly depolarized the membrane potential by approximately 20 mV, whereas these cells were hyperpolarized approximately 10 mV by DA (10 microM) and approximately 14 mV by the GABAB-receptor agonist baclofen (30 microM). High-speed chronoamperometric recordings were used to monitor clearance properties of exogenously applied DA signals during similar manipulations. Superfusion of slices with 15 mM KCl significantly increased the time course of the DA signal, consistent with inhibition of DAT activity. Application of the D2 DA-receptor antagonist sulpiride (50 microM) also significantly increased the time course, suggesting that DA-induced hyperpolarization enhances DAT activity. Baclofen reversed the effects of sulpiride on DA clearance. These results demonstrate that changes in DA cell membrane potential can modulate DAT activity.

Animals↗

PubMed1999

Microdialysis studies of basal levels and stimulus-evoked overflow of dopamine and metabolites in the striatum of young and aged Fischer 344 rats.

The technique of intracranial microdialysis was used to investigate the effects of aging on the striatal dopaminergic system of the anesthetized Fischer 344 rat. Microdialysis probes were implanted into the striatum of young (2-8 months) and aged (24-28 months) urethane anesthetized rats. Striatal dialysate levels were analyzed for dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and serotonin (5-HT) by high performance liquid chromatography with electrochemical detection. As compared to the young animals, basal extracellular levels of DA and DOPAC were significantly decreased in two groups of aged animals. Stimulation with excess potassium added through the microdialysis probe produced a robust overflow of DA in the young and aged rat striatum, but the evoked overflow of DA was not diminished in the aged rat striatum as compared to young animals. In contrast, d-amphetamine-evoked overflow of DA was again robust in young and aged animals, but was greatly decreased in the aged rat striatum as compared to the signals recorded in the young rats. Taken together with previous reports, these data support the hypothesis that a major change in the regulation of DA release that occurs in aging involves changes in the function of the neuronal uptake of DA, which may be a compensatory property of DA neurons in senescence.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1999

Dopamine D2 receptor-deficient mice exhibit decreased dopamine transporter function but no changes in dopamine release in dorsal striatum.

Presynaptic D2 dopamine (DA) autoreceptors, which are well known to modulate DA release, have recently been shown to regulate DA transporter (DAT) activity. To examine the effects of D2 DA receptor deficiency on DA release and DAT activity in dorsal striatum, we used mice genetically engineered to have two (D2+/+), one (D2+/-), or no (D2-/-) functional copies of the gene coding for the D2 DA receptor. In vivo microdialysis studies demonstrated that basal and K+-evoked extracellular DA concentrations were similar in all three genotypes. However, using in vivo electrochemistry, the D2-/- mice were found to have decreased DAT function, i.e., clearance of locally applied DA was decreased by 50% relative to that in D2+/+ mice. In D2+/+ mice, but not D2-/- mice, local application of the D2-like receptor antagonist raclopride increased DA signal amplitude, indicating decreased DA clearance. Binding assays with the cocaine analogue [3H]WIN 35,428 showed no genotypic differences in either density or affinity of DAT binding sites in striatum or substantia nigra, indicating that the differences seen in DAT activity were not a result of decreased DAT expression. These results further strengthen the idea that the D2 DA receptor subtype modulates activity of the striatal DAT.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1999

Age-related reductions in [3H]WIN 35,428 binding to the dopamine transporter in nigrostriatal and mesolimbic brain regions of the fischer 344 rat.

In the present study, we used the potent cocaine analog [3H]WIN 35, 428 to map and quantify binding to the dopamine transporter (DAT) within the dorsal striatum, nucleus accumbens, substantia nigra, and ventral tegmental area in young (6-month-old), middle-aged (12-month-old), and aged (18- and 24-month-old) Fischer 344 rats. Quantitative autoradiographic analysis of indirect [3H]WIN 35,428 saturation curves revealed two-site binding for all four brain regions in every age group. The percentage of binding to the high- or low-affinity sites did not differ with age or region and was approximately 50%. However, significant age-related decreases in the overall density (Bmax) of [3H]WIN 35,428-binding sites were observed in the striatum, nucleus accumbens, substantia nigra, and ventral tegmental area. The Bmax within all brain regions declined by more than 15% every 6 months, with the Bmax in the aged (24-month-old) group being approximately half that measured in the young adult (6-month-old) group. Competition experiments indicated that nomifensine also exhibited two-site binding to the DAT in Fischer 344 rats. No consistent age-related differences in binding affinities were noted with either [3H]WIN 35,428 or nomifensine. Taken together, these results support the hypothesis that functional DATs within the nigrostriatal and mesolimbic systems are down-regulated with age, without changing their affinity for ligands.

Age Factors↗

PubMed1999

In vivo dopamine clearance rate in rat striatum: regulation by extracellular dopamine concentration and dopamine transporter inhibitors.

Dopamine transporter (DAT) inhibitors are expected to decrease dopamine (DA) clearance from the extracellular space of the brain. However, mazindol and cocaine have been reported to "anomalously" increase DA clearance rate. To better understand in vivo DAT activity both in the absence and presence of DAT inhibitors, clearance of exogenously applied DA was measured in dorsal striata of urethane-anesthetized rats using high-speed chronoamperometry. As higher amounts of DA were ejected, DA signal amplitudes, but not time courses, increased. Clearance rates increased until near maximal rates of 0.3 to 0.5 microM/s were attained. Provided baseline clearance rates were relatively low (< 0.1 microM/s), local application of either nomifensine or cocaine markedly increased exogenous DA signal amplitudes and time courses. Relative to the low baseline group, locally applied nomifensine decreased clearance rate when baseline clearance was high ( approximately 0.4 microM/s). However, even when baseline clearance rates were high, systemic injection of nomifensine, mazindol, GBR 12909, or benztropine increased DA signal amplitudes to a greater extent than time courses, consistent with the observed increases in clearance rates. In contrast, despite low baseline clearance rates, systemic injection of cocaine, WIN 35,428, or d-amphetamine preferentially increased DA signal time course, consistent with the observed decreases in clearance rates. Our results emphasize that as extracellular DA concentrations increase, DAT velocity increases to a maximum, partially explaining the ability of DAT inhibitors to increase DA clearance rates. However, by itself, kinetic activation is not sufficient to explain the ability of certain systemically administered DAT inhibitors to anomalously increase DA clearance.

Animals↗

PubMed1999

Differences in pharmacological properties of dopamine release between the substantia nigra and striatum: an in vivo electrochemical study.

The properties of dopamine (DA) release in the rat substantia nigra (SN) and striatum were investigated using high-speed chronoamperometric recordings in brain slices. In both brain regions, a 2-min bath superfusion with 30 mM KCl produced robust DA-like electrochemical signals, with the mean amplitude of the signal being >10-fold greater in the striatum than the SN. The reproducibility of the response was confirmed by a second stimulus (S2)/first-stimulus (S1) ratio of >0.8 in both regions. The bath application of tetrodotoxin significantly reduced the S2/S1 ratio in both the striatum and SN, implicating the requirement for voltage-sensitive sodium channels in the DA-release process. However, the application of cadmium chloride, a nonselective blocker of voltage-sensitive calcium channels, reduced the S2/S1 ratio only in the striatum and not within the SN. Moreover, removal of Ca2+ from the buffer did not significantly affect release within the SN, despite a >85% reduction in release within the striatum. In addition, although the D2 receptor antagonist sulpiride enhanced the S2/S1 ratio in the striatum, no effect of this agent was seen in the SN. Finally, the application of d-amphetamine produced DA-like electrochemical signals in both the striatum and SN. However, the amplitude of the d-amphetamine-evoked response, relative to the KCl-evoked release, was much smaller in the striatum than in the SN. Taken together, these data support the hypothesis that differences in the mechanism or mechanisms of release exist between somatodendritic and axonal elements within the nigrostriatal pathway.

Animals↗

PubMed1999

Age-related changes in the capacity, rate, and modulation of dopamine uptake within the striatum and nucleus accumbens of Fischer 344 rats: an in vivo electrochemical study.

Age-related changes in the capacity, rate, and modulation of dopamine (DA) uptake within the striatum and the nucleus accumbens core of Fischer 344 rats were investigated using in vivo electrochemical recordings coupled with local drug application techniques. Equimolar amounts of DA were pressure ejected into the striatum and the nucleus accumbens of 6-, 12-, 18-, and 24-month old rats. The DA ejections produced larger DA signal amplitudes in the older rats, suggesting age-related differences in the capacity to clear extracellular DA. Within the striatum, the capacity and rate of DA uptake were reduced by 50% in the aged groups (18 and 24 months) compared with the younger rats (6 and 12 months). In the nucleus accumbens, significant reductions in DA uptake capacity and rate were observed in the 24-month group. In both brain regions and in all age groups studied, the rate of DA uptake was found to be concentration-dependent until a maximal rate was reached. The maximum rate of DA transport was significantly reduced in both the striatum and the nucleus accumbens of aged rats (18 and 24 months versus 6 and 12 months). The ability of nomifensine, an inhibitor of the DA transporter, to modulate DA signal amplitudes in the striatum and the nucleus accumbens was also decreased with age (24 months versus 6 months). Taken together, these findings demonstrate substantial age-related deficits in DA uptake processes within the striatum and the nucleus accumbens, consistent with the hypothesis that DA uptake may be slowed in aged animals to compensate for reductions in DA release.

Adrenergic Uptake Inhibitors↗

PubMed1998

Nicotine-evoked nitric oxide release in the rat hippocampal slice.

The effects of cholinergic agonists on nitric oxide (NO) release in hippocampal slices from male Sprague-Dawley rats were investigated using electrochemical recording procedures using Nafion and O-phenylenediamine-treated carbon fiber microelectrodes. These microelectrodes are highly selective for NO versus other interferents. Acetylcholine (Ach) with neostigmine, or nicotine was delivered by pressure ejection from pipettes placed within 300 microm of the NO sensors. Both Ach and nicotine produced NO signals ranging from 0.04 to 2.14 microM in the CA1, CA3, and dentate gyrus of the rat hippocampus that lasted for 2-5 min. The Ach responses were not antagonized by the muscarinic antagonist atropine. However, nicotine-evoked responses were partially antagonized by alpha-bungarotoxin, a finding consistent with alpha7-nicotinic cholinergic receptors being involved with the effects of nicotine. These data support the hypothesis that nicotine is capable of evoking long lasting NO release in the hippocampus.

Acetylcholine↗

PubMed1998

Normal and drug-induced locomotor behavior in aging: comparison to evoked DA release and tissue content in fischer 344 rats.

The consequences of aging on dopamine (DA) regulation within the nigrostriatal and mesolimbic systems were investigated with a combination of behavioral, in vivo electrochemical, and high-performance liquid chromatography measurements using 6-, 12-, 18- and 24-month old male Fischer 344 (F344) rats. Spontaneous locomotor testing demonstrated that aged (18- and 24-month) rats moved significantly less and at a slower speed than younger (6- and 12-month) animals. Additionally, systemic injection (intraperitoneal) of the DA uptake inhibitor, nomifensine, was significantly less efficacious in augmenting the locomotor activity of aged rats compared to the younger animals. Age-dependent alterations in the release capacity of DA neurons within the regions involved in movement were investigated using in vivo electrochemistry. These recordings indicated that both the magnitude and temporal dynamics of potassium (70 mM)-evoked DA overflow were affected by the aging process. Signal amplitudes recorded in the 24-month rats were 30-60% reduced in both the striatum and nucleus accumbens as compared to the young adult groups. In addition, the duration of the electrochemical DA signals recorded within the striatum of 24-month old rats was twice that in the younger animals (6- and 12-month). Whole tissue measurements of DA and DA metabolites suggest age-related deficits in locomotion and DA release were not related to decreases in the storage or synthesis of DA within the striatum, nucleus accumbens, substantia nigra, ventral tegmental area or medial prefrontal cortex. Taken together, these results indicate age-dependent deficits in movement are related to the dynamic properties of DA release and not static measures of DA content.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1998

Locomotor activity in D2 dopamine receptor-deficient mice is determined by gene dosage, genetic background, and developmental adaptations.

Locomotor activity is a polygenic trait that varies widely among inbred strains of mice (). To characterize the role of D2 dopamine receptors in locomotion, we generated F2 hybrid (129/Sv x C57BL/6) D2 dopamine receptor (D2R)-deficient mice by gene targeting and investigated the contribution of genetic background to open-field activity and rotarod performance. Horizontal activity of D2R-/- mice was approximately half that of drug-naive, strain-matched controls but was significantly greater than haloperidol-treated controls, which were markedly hypokinetic. Wild-type 129/SvEv and C57BL/6 mice with functional D2 receptors had greater interstrain differences in spontaneous activity than those among the F2 hybrid mutants. Incipient congenic strains of D2R-deficient mice demonstrated an orderly gene dosage reduction in locomotion superimposed on both extremes of parental background locomotor activity. In contrast, F2 hybrid D2R-/- mice had impaired motor coordination on the rotarod that was corrected in the congenic C57BL/6 background. Wild-type 129/SvEv mice had the poorest rotarod ability of all groups tested, suggesting that linked substrain 129 alleles, not the absence of D2 receptors per se, were largely responsible for the reduced function of the F2 hybrid D2R-/- and D2R+/- mice. Neurochemical and pharmacological studies revealed unexpectedly normal tissue striatal monoamine levels and no evidence for supersensitive D1, D3, or D4 dopamine receptors in the D2R-/- mice. However, after acute monoamine depletion, akinetic D2R+/- mice had a significantly greater synergistic restoration of locomotion in response to SKF38393 and quinpirole compared with any group of D2R+/+ controls. We conclude that D2R-deficient mice are not a model of Parkinson's disease. Our studies highlight the interaction of multiple genetic factors in the analysis of complex behaviors in gene knock-out mice.

Adaptation, Physiological↗

PubMed1998

Age-related decline in striatal dopamine release and motoric function in brown Norway/Fischer 344 hybrid rats.

The Brown Norway/Fischer 344 F1 hybrid rats (F344BNF1) is a newer rat model and is emerging as an important rodent model of aging. In the present study we used motoric performance tests, intracerebral microdialysis, and neurochemical measures of postmortem brain tissue to investigate the effects of aging in young (4-5 months), middle-aged (18-19), and old (24-25 months) F344BNF1 hybrid rats. We observed that old F344BNF1 rats exhibited decreased motoric performance, and lower levels of spontaneous and d-amphetamine-induced locomotor activity than those observed in young F344BNF1 rats. Microdialysis measures of extracellular basal levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 4-hydroxy-3-methoxyphenylacetic acid (HVA) were significantly diminished in the striata of the middle-aged and old rats as compared to levels in young animals. In addition, d-amphetamine-evoked overflow of DA was significantly decreased in the middle-aged and aged rat striatum as compared to DA overflow in young F344BNF1 rats. Studies of postmortem brain tissue showed that the changes in overflow of DA correlated with significantly lower DA tissue content in ventral striatum and midbrain. Moreover, both dopamine turnover ratios (DOPAC/DA, HVA/DA) and the serotonin turnover ratio (5-HIAA/5-HT) were significantly elevated in the ventral striatum and nucleus accumbens. The results of this study demonstrate a correlation between reductions in striatal DA neurochemistry and diminished motor function in aged F344BNF1 rats.

Aging↗

PubMed1998

In vivo electrochemical studies of dopamine clearance in subregions of rat nucleus accumbens: differential properties of the core and shell.

The dopamine (DA) uptake/clearance properties of the DA transporter (DAT) in the core and shell of the nucleus accumbens were measured using in vivo electrochemical recordings. Calibrated amounts of a DA solution were pressure-ejected from a micropipette/electrode assembly placed in the core or shell of the nucleus accumbens in anesthetized male Fischer 344 rats. Initial studies in the two brain regions revealed that the core and shell have different DA clearance properties as measured by the extracellular DA signal amplitudes, clearance times, and clearance rates. Although the same number of picomoles of DA were applied, DA clearance signals recorded in shell had significantly greater amplitudes but faster clearance rates than those recorded in the core. Systemic administration of 20 mg/kg cocaine, a monoamine transporter inhibitor, greatly increased the signal amplitude from the locally applied DA in both the core and shell. Signal amplitudes were increased to a greater extent in the shell, compared with the core, after cocaine administration. However, cocaine affected the clearance time of DA only in the core and the DA clearance rate only in the shell. Taken together with previously reported data, these studies further support differential activity of the DAT in the core versus shell subregions of the nucleus accumbens. In addition, these data indicate that DATs are more sensitive to the effects of psychomotor stimulants, such as cocaine, in the shell of the nucleus accumbens.

Animals↗