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J F Marshall

Publications and source records attributed to J F Marshall.

At least 73 records · Page 4Linked to original sources
PubMed1995

D1-class dopamine receptor involvement in the behavioral recovery from prefrontal cortical injury.

Following unilateral aspiration of the left medial agranular cortex (AGm) region of prefrontal cortex, rats demonstrate contralateral neglect, characterized by a failure to orient to visual, tactile and auditory stimuli presented on the contralateral body side. While dopamine (DA) has been implicated in cortical neglect and its recovery, this study specifically examined D1-class DA receptors for their involvement in spontaneous recovery from neglect caused by AGm ablation. In the first experiment, left AGm-ablated rats demonstrated severe neglect of contralateral stimuli of each modality which spontaneously recovered over a period of several weeks. Recovered rats were given 7.0 micrograms/kg (s.c.) of the D1-selective antagonist SCH 23390. SCH 23390 reinstated severe neglect of contralateral stimuli, yet had no effect on orientation to ipsilateral stimuli. The same dose had no effect on the orientation behavior of controls. In a second experiment, D1 receptor characteristics were quantified via binding of [3H]SCH 23390 to tissue homogenates of the caudate-putamen of recovered AGm-ablated rats. Numbers and affinities of striatal D1 receptors of rats with unilateral AGm ablations did not differ between hemispheres or from values obtained from lesioned controls. Considered together, these findings indicate that recovery from neglect produced by cortical injury is associated with an increased dependence on D1-class receptor-mediated events, and that this increased dependence is unlikely to be mediated through changes in D1-class receptor numbers or affinities within caudate-putamen.

Animals↗
PubMed1995

D1 dopamine receptors influence Fos immunoreactivity in the globus pallidus and subthalamic nucleus of intact and nigrostriatal-lesioned rats.

Studies of the globus pallidus (GP) and subthalamic nucleus (STN) have emphasized the role of D2 dopamine receptors, although effects of D1 receptor activation on GP firing rate and STN metabolism have been reported, especially in rats with nigrostriatal lesions. This study systematically investigated the effects of D1 and D2 receptor activation on the activity of the GP and STN in intact and 6-OHDA-lesioned rats using immunostaining for the immediate-early gene Fos. In intact rats, the D1 agonist SKF 38393 (20.0 mg/kg) produced a five-fold potentiation of the GP Fos expression due to the D2 agonist quinpirole produced significant Fos expression. In rats with prior nigrostriatal lesions, SKF 38393 (4.0 or 20.0 mg/kg) increased Fos immunostaining in both the GP and STN, while quinpirole increased it only in the GP. SKF 38393 effects in the GP and STN of nigrostriatal-lesioned rats were blocked completely by SCH 23390, and unaffected by eticlopride. These results are a novel demonstration of control of Fos expression by dopaminergic drugs in the STN and by D1 agonists in the GP.

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

Damage to dopamine systems differs between Parkinson's disease and Alzheimer's disease with parkinsonism.

Parkinsonism occurs in approximately 35 to 40% of patients with Alzheimer's disease (AD) even with little or no neuronal degeneration in the substantia nigra, which in idiopathic Parkinson's disease (PD) results in the severe loss of striatal dopamine transporter sites. It is not known if there is a loss of striatal dopamine transporter sites in AD with coexistent parkinsonism (AD/parkinsonism). We quantified the pattern of these sites in the striatum and midbrain of patients with the clinical diagnosis of PD, AD, and AD/parkinsonism in comparison with a group of age-matched control subjects. We also quantified the number of D2 receptors and the levels of tyrosine hydroxylase in the substantia nigra and ventral tegmental area of the same groups. The results showed that in AD the loss of dopamine transporter sites was restricted to the nucleus accumbens. The loss of these sites in the AD/parkinsonism group was more extensive than in the AD group, with the most severe losses in the rostral caudate and putamen and least in the caudal caudate and putamen. While the PD group showed an equally severe reduction in numbers of sites, the caudal to rostral gradient of loss differed from that in the AD/parkinsonism group. The PD group also showed a marked loss of dopamine transporter sites, tyrosine hydroxylase, and D2 autoreceptors (located on dopamine neurons) in the substantia nigra and ventral tegmental area. In contrast, no reductions in dopamine transporter sites, tyrosine hydroxylase, and D2 autoreceptors were observed in the substantia nigra and ventral tegmental area of the AD or AD/parkinsonism groups. Thus, the loss of striatal dopamine transporter sites in AD/parkinsonism may be related to the clinical parkinsonian symptoms. However, the loss is not simply the result of neuronal degeneration in the substantia nigra, but must derive from other processes.

Aged↗
PubMed1995

Time-dependent changes in dopamine agonist-induced striatal Fos immunoreactivity are related to sensory neglect and its recovery after unilateral prefrontal cortex injury.

This study examined interactions between the corticostriatal glutamatergic system and the nigrostriatal dopaminergic system via immunocytochemical examination of dopamine (DA) agonist induction of the striatal immediate early gene product Fos following cortical injury. After unilateral aspiration of the medial agranular cortex (AGm) region of prefrontal cortex, rats were tested for orientation to visual, tactile, and auditory stimuli. Fos immunoreactivity induced by d-amphetamine (5 mg/kg) or apomorphine (5 mg/kg) was quantified in dorsolateral and ventrolateral regions of caudate-putamen (CPu) in rats still demonstrating sensory neglect (5 days postsurgery) and in rats recovered from sensory neglect produced by AGm ablation (29+ days postsurgery). The pattern of immunoreactivity of rats still demonstrating neglect differed from that of unlesioned rats or recovered AGm-ablated rats. In rats demonstrating sensory neglect, d-amphetamine or apomorphine induction of Fos in the ipsilateral CPu was reduced by about 40% compared to the contralateral CPu or to comparable readings in unlesioned controls. These asymmetries were restricted to dorsolateral CPu, the region receiving the densest input from AGm. In contrast, recovered AGm-ablated rats had DA agonist-induced striatal Fos immunoreactivity that was symmetrical between the two hemispheres and comparable to control values. These findings indicate that adaptations involving the striatal medium spiny neuron, a site of convergence of cortical glutamatergic and nigral dopaminergic afferents, may contribute to recovery from behavioral deficits resulting from neocortical injury.

Animals↗
PubMed1995

Alpha v beta 1 is a receptor for vitronectin and fibrinogen, and acts with alpha 5 beta 1 to mediate spreading on fibronectin.

We have shown previously that VUP was the only line out of ten human melanoma lines that failed to express the vitronectin receptor alpha v beta 3, but instead expressed alpha v beta 1. Levels of alpha v beta 1 expression were low on parental VUP cells so that iterative sorting by FACS, using an anti-alpha v antibody (13C2), was utilised to derive sublines with 8- to 10-fold higher amounts of cell surface alpha v beta 1. There was little difference between low (V-) and high (V+) alpha v beta 1-expressing sublines with regard to adherence to collagen type I, collagen type IV or laminin substrata. However, adherence to vitronectin and fibrinogen correlated closely with alpha v beta 1 expression (35-42% adhesion for V(+) lines versus 6-8% adhesion for V- lines on vitronectin, for example). Utilising a high alpha v beta 1-expressing subline (V + B2) we have shown that binding to vitronectin and fibrinogen was inhibited specifically by function-blocking antibodies to alpha v (17E6 and 14D9) and beta 1 (A11B2). V(+) sublines spread more compared with V(-) sublines on both vitronectin and fibronectin. However, neither alpha 5- nor alpha v-blocking antibodies had any effect on attachment or spreading of V + B2 on fibronectin whereas the combination of alpha 5 (PID6)- and alpha v(17E6)-blocking antibodies abrogated binding to fibronectin almost completely. This is the first report of an alpha v beta 1 integrin able to recognize vitronectin and fibrinogen, and also cooperate with alpha 5 beta 1 to mediate attachment to and spreading on fibronectin.

Antibodies↗
PubMed1994

Rapid development of D1 and D2 dopamine receptor supersensitivity as indicated by striatal and pallidal Fos expression.

Rats were injected with a single dose of the monoamine-depleting agent reserpine (5 mg/kg s.c.) or its vehicle. Twenty-four hours later rats were injected with either the selective D1 agonist SKF 38393 (5 mg/kg i.p.), the selective D2 agonist quinpirole (0.1 mg/kg i.p.) or saline, and perfused 2 h later. Fos-like immunoreactivity was visualized using a polyclonal antibody to the Fos protein and standard ABC methods. Reserpine rendered striatal D1 and D2 receptors supersensitive as indicated by 10- to 12-fold increases in striatal and pallidal Fos immunoreactivity. The short latency of the development of both D1 and D2 supersensitivity limits the candidate causative mechanisms to those that occur within hours of the initiating stimulus.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1994

Amphetamine- and cocaine-induced fos in the rat striatum depends on D2 dopamine receptor activation.

Amphetamine or cocaine injection causes expression of the immediate-early gene c-fos in the striatum. Previous studies have shown that dopamine D1 receptor activation is necessary for this effect, but have not established a consistent role for D2 receptors. We have investigated the involvement of D2 receptors in indirect dopamine agonist-induced striatal Fos-like immunoreactivity using the selective D2 antagonist eticlopride. Eticlopride treatment (0.5 mg/kg) caused Fos expression by itself, but also decreased Fos expression in the central striatum due to amphetamine (5.0 mg/kg) or cocaine (40 mg/kg) by 90% and 85%, respectively. In striatonigral neurons, identified by labeling with the retrograde tracer Fluorogold iontophoresed into the substantia nigra pars reticulata, the blockade of stimulant-induced Fos-like immunofluorescence by eticlopride was nearly complete, with decreases of 98% for amphetamine and 94% for cocaine. In striatonigral neurons, the D2 antagonist alone had minimal effect. We conclude that activation of both D1 and D2 receptor classes by dopamine agonists is necessary for induction of Fos in the striatonigral cells of normal rats. These results provide an important parallel to behavioral and electrophysiological work that also demonstrates D1/D2 interdependence in the control of normal basal ganglia functions.

Amphetamines↗
PubMed1994

Excitotoxic striatal lesions protect against subsequent methamphetamine-induced dopamine depletions.

Repeated administration of methamphetamine (m-AMPH) produces a prolonged elevation of extracellular dopamine (DA) levels in rat striatum and subsequent damage to striatal DA terminals. In the present study, a unilateral striatal infusion of quinolinic acid (QA) (15 ug/0.5 microliter) 2 weeks before repeated m-AMPH treatment (four injections of 4 mg/kg, s.c., at 2-hr intervals) protected that striatum from m-AMPH-induced DA terminal injury. One week after m-AMPH treatments, striatal DA contents were substantially below control values in the vehicle-infused striata, whereas the DA contents of the QA-infused striata were equal to those of animals not exposed to m-AMPH. The QA infusions alone injured striatal neurons, as indicated by decreased [3H]SCH 23390 and [3H]spiroperidol binding to D1 and D2 receptors, respectively. However, QA infusions by themselves did not significantly change the DA content or [3H]mazindol binding to the high-affinity DA transporter of the infused striata 3 weeks later. In vivo microdialysis was performed in the previously QA- or vehicle-infused striata during regimens of repeated m-AMPH or saline treatments. QA infusions that were effective in protecting against m-AMPH neurotoxicity did not significantly reduce stimulant-induced DA overflow, compared with the overflow that occurred in the vehicle-infused striata of m-AMPH-treated rats. Thus m-AMPH-induced DA overflow appears to be dissociated from the resulting DA terminal injury in the QA-infused striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Selective increase of NMDA-sensitive glutamate binding in the striatum of Parkinson's disease, Alzheimer's disease, and mixed Parkinson's disease/Alzheimer's disease patients: an autoradiographic study.

Parkinson's disease (PD) and Alzheimer's disease (AD) may share certain abnormalities since a subset of PD patients suffer from dementia, and some AD individuals show extrapyramidal symptoms. In vitro quantitative autoradiography was used to examine different subtypes of excitatory amino acid (EAA) receptors (NMDA, KA, and AMPA) and dopamine transporter sites in the striatum (caudate, putamen) and nucleus accumbens (NAc) from idiopathic PD, pure AD, and mixed PD/AD patients. PD and AD groups, and to a lesser extent the PD/AD groups, showed substantially increased binding to NMDA receptors in the striatum and NAc. No statistically significant changes in binding to KA and AMPA receptors were found in any patient group. 3H-mazindol binding to dopamine transporter sites was significantly decreased in the striatum and NAc of PD and PD/AD patients, but only in the putamen and NAc of AD patients. The data indicate that (1) the majority of striatal EAA receptors are not located on dopaminergic nigrostriatal nerve terminals, and (2) elevated binding to striatal NMDA receptors correlates with binding to dopamine transporter sites in PD patients, but not in AD and PD/AD individuals. Thus, the mechanisms of NMDA receptor changes in the striatum of AD and PD patients may be different. However, it is postulated that increased binding to NMDA receptors in Parkinson and Alzheimer striatum occurs in response to an insult(s) within the striatothalamocortical circuits and that this may contribute to the clinical similarities described for subsets of PD and AD patients.

Aged↗
PubMed1993

Dopamine D2 receptor control of pallidal fos expression: comparisons between intact and 6-hydroxydopamine-treated hemispheres.

Fos expression in the globus pallidus (GP) of rats was elicited by the D2 agonist quinpirole both ipsilateral and contralateral to a unilateral nigrostriatal 6-hydroxydopamine (6-OHDA) injection; however, the 6-OHDA-treated hemisphere was more sensitive to this effect. The quinpirole-induced GP Fos expression was antagonized in both hemispheres by the D2 antagonist eticlopride, but not by the D1 antagonist SCH 23390. In neurologically intact rats, the D1 agonist SKF 38393, which alone did not elicit pallidal Fos expression, augmented the quinpirole-induced Fos response. Thus, D1 agonists can synergize with D2 agonists in inducing GP c-fos; but the D2-stimulated induction does not depend on concurrent D1 agonism.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

L-dopa pretreatment potentiates striatal dopamine overflow and produces dopamine terminal injury after a single methamphetamine injection.

Rats receiving L-dopa/carbidopa (70 mg/kg/17.5 mg/kg, i.p.) 1 h prior to a single methamphetamine (m-AMPH) (4 mg/kg, s.c.) pretreatment showed an extraordinary striatal dopamine (DA) overflow into the extracellular space (30-60 times basal overflow) as compared to the DA overflow elicited by m-AMPH alone (4-5 times basal). Animals treated with L-dopa/carbidopa plus m-AMPH, but not m-AMPH alone, had substantial (60%) decreases in striatal DA content 1 week later. These findings support the conclusion that the magnitude of m-AMPH-induced DA overflow contributes to the degree of nerve terminal damage and highlight the importance of extracellular DA in striatal terminal damage.

Analysis of Variance↗
PubMed1993

Striatal Fos expression is indicative of dopamine D1/D2 synergism and receptor supersensitivity.

Immediate-early genes, such as c-fos, are responsive to dopaminergic stimulation in the brain and can have prolonged effects on the transcription of other genes. Thus, they may mediate some of the long-term consequences of altered dopaminergic transmission on striatal neurons, such as the supersensitivity to dopamine and its agonists that occurs in response to dopamine denervation. The two dopamine receptor families, D1 and D2, interact synergistically under normal conditions but independently after treatments that induce pronounced supersensitivity to dopamine agonists. Using immunocytochemical methods in rats treated with directly acting selective dopamine agonists, we have determined that dopamine-mediated expression of Fos and Fos-like antigens in the striatum normally requires concomitant stimulation of D1 and D2 receptors. Separate administration of a high dose of a selective D1 (SKF 38393; 20 mg/kg) or D2 (quinpirole; 3 mg/kg) agonist induced Fos-like immunoreactivity in few neurons, whereas combined administration of the D1 and D2 agonists produced patches of intensely stained immunoreactive nuclei in the caudate-putamen. Repeated administration of reserpine (1 mg/kg per day for 5 days), which causes supersensitivity to dopamine agonists and a breakdown in D1/D2 synergism behaviorally, also causes a change in control of c-fos, such that independent stimulation of D1 receptors by SKF 38393 (20 mg/kg) elicited pronounced Fos-like immunoreactivity in the striatum; combined treatment with SKF 38393 (20 mg/kg) and quinpirole (3 mg/kg) in reserpine-treated rats elicited Fos-like expression in no more neurons than did D1 agonism alone. These data demonstrate that dopamine-mediated Fos expression in the striatum is indicative of the state of D1/D2 synergism and receptor supersensitivity.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

The role of dopamine in the maintenance and breakdown of D1/D2 synergism.

The neurochemical factors involved in the maintenance and breakdown of dopamine D1/D2 receptor synergism were investigated by giving rats various pharmacological treatments that diminish the ability of dopamine to interact with its D1 and/or D2 receptors. Following these treatments, rats were observed for the expression of stereotyped motor behavior in response to independent stimulation of D1 or D2 receptors. Independent D2-mediated responses were observed: (a) 2 h after the last of three daily reserpine (1 mg/kg) injections, (b) 48 h after bilateral 6-hydroxydopamine (6-OHDA) lesions of the mesostriatal pathways, (c) 24 h after a concentrated 48-h regimen (one injection/6 h) of eticlopride (0.5 mg/kg) or eticlopride+SCH 23390 (0.5 mg each), and (d) 2 h after a concentrated 48-h regimen (one injection/6 h) of alpha-methyl-p-tyrosine (alpha MPT; 100 mg/kg), but not after control treatments or a concentrated regimen of SCH 23390 alone. By contrast, independent D1-mediated responses were observed only after three daily reserpine injections or 48 h after bilateral 6-OHDA lesions. Independent D1-mediated stereotypy was not observed under control conditions or following a concentrated 48-h regimen of (a) SCH 23390 or eticlopride (0.5 mg/kg each) alone or in combination, (b) a high dose of SCH 23390 (1.0 mg/kg), (c) alpha MPT (100 mg/kg), or (d) alpha MPT (100 mg/kg)+SCH 23390 (1.0 mg/kg). Reserpine, bilateral 6-OHDA, and alpha MPT treatments produced striatal dopamine depletions of 96%, 92%, and 71%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Dopamine-glutamate interactions in methamphetamine-induced neurotoxicity.

Repeated administration of methamphetamine (m-AMPH) to rats induces dopamine (DA) terminal damage, and coadministration of antagonists of the N-methyl-D-aspartate (NMDA) or dopamine D1 or D2 receptors are protective. Striatal microdialysis of rats given a neurotoxic regimen of 4 x m-AMPH (4 mg/kg, s.c.) treatments revealed a dramatic and prolonged elevation of extracellular DA after the final m-AMPH administration. Neuroprotective regimens of MK-801, SCH 23390, or eticlopride greatly attenuated the overflow of DA resulting from the fourth m-AMPH treatment. By itself, MK-801 had no significant influence on striatal DA overflow, whereas either DA antagonist given alone elevated dialysate DA concentrations. A significant correlation was found between the magnitude of the m-AMPH-induced DA overflow of individual microdialyzed rats and their striatal DA content at sacrifice one week later. We conclude that the ability of non-competitive NMDA antagonists and of the D1 or D2 antagonists to protect against m-AMPH-induced striatal DA terminal injury can be accounted for by their attenuation of m-AMPH-evoked DA overflow. These findings underscore the important role played by elevated extracellular DA concentrations to the injurious effects of this stimulant drug.

Animals↗
PubMed1993

Methamphetamine-induced dopamine overflow and injury to striatal dopamine terminals: attenuation by dopamine D1 or D2 antagonists.

Pharmacological blockade of either D1 or D2 dopamine (DA) receptors prevents damage of striatal DA terminals by repeated doses of methamphetamine (m-AMPH). Because the substantial DA overflow produced by multiple m-AMPH treatments appears to contribute to the subsequent injury, we have investigated the effects of blockade of D1 or D2 receptors on m-AMPH-induced DA efflux using in vivo microdialysis. Four treatments with m-AMPH (4 mg/kg, s.c., 2-h intervals) produced large increases in striatal DA overflow, with particularly marked overflow (10 times the basal values) following the fourth injection. Administered by themselves, four injections of the D1 antagonist SCH 23390 or the D2 antagonist eticlopride (0.5 mg/kg, i.p., 2-h intervals) significantly increased striatal DA overflow. However, treatment with either SCH 23390 or eticlopride 15 min before each of four m-AMPH injections attenuated the marked DA peak otherwise seen after the fourth m-AMPH injection. These effects on DA overflow were related to subsequent DA depletions. Although our m-AMPH regimen produced a 54% reduction in striatal DA tissue content 1 week later, pretreatments with either the D1 or the D2 antagonist completely prevented subsequent DA content depletions. Furthermore, the DA content of striatal tissue remaining 1 week after m-AMPH treatment was significantly correlated with the magnitude of the cumulative DA overflow during the m-AMPH treatment (r = -0.69). Thus, the extensive DA overflow seen during neurotoxic regimens of m-AMPH appears critical to the subsequent neurotoxicity, and the neuroprotective action of DA receptor antagonists seems to result from their attenuation of stimulant-induced DA overflow.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Striatal subregions are differentially vulnerable to the neurotoxic effects of methamphetamine.

Methamphetamine (m-AMPH) or saline was repeatedly administered to rats. One week later, the caudate-putamen of the m-AMPH-treated rats revealed a decrease in both [3H]mazindol-labeled dopamine uptake sites and tissue dopamine content. Moreover, the resulting pattern of decline in these measures was regionally heterogeneous. The ventral caudate-putamen displayed the greatest decrease in both [3H]mazindol binding and dopamine content while the neighboring nucleus accumbens and the dorsal caudate-putamen remained relatively intact. These results indicate a regional difference in the susceptibility of striatal dopaminergic terminals to the neurotoxic effects of methamphetamine.

Animals↗