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E D Abercrombie

Publications and source records attributed to E D Abercrombie.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1995

Biochemistry of somatodendritic dopamine release in substantia nigra: an in vivo comparison with striatal dopamine release.

The somatodendritic release of dopamine in substantia nigra previously has been suggested to be nonvesicular in nature and thus to differ from the classical, exocytotic release of dopamine described for the dopaminergic nerve terminal in striatum. We have compared the effects of reserpine, a compound that disrupts vesicular sequestration of monoamines, on the storage and release of dopamine in substantia nigra and striatum of rats. Reserpine administration (5 mg/kg, i.p.) significantly decreased the tissue level of dopamine in substantia nigra pars reticulata, substantia nigra pars compacta, and striatum. In these brain areas, reserpine-induced reductions in tissue dopamine level occurred within 2 h and persisted at 24 h postdrug. In vivo measurements using microdialysis revealed that reserpine administration rapidly decreased the extracellular dopamine concentration to nondetectable levels in substantia nigra as well as in striatum. In both structures, it was observed that reserpine treatment significantly attenuated the release of dopamine evoked by a high dose of amphetamine (10 mg/kg, i.p.) given 2 h later. In contrast, dopamine efflux in response to a low dose of amphetamine (2 mg/kg, i.p.) was not altered by reserpine pretreatment either in substantia nigra or in striatum. The present data suggest the existence, both at the somatodendritic and at the nerve terminal level, of a vesicular pool of dopamine that is the primary site of transmitter storage and that can be displaced by high but not low doses of amphetamine. The physiological release of dopamine in substantia nigra and in striatum is dependent on the integrity of this vesicular store.

Amphetamine↗
PubMed1994

L-3,4-dihydroxyphenylalanine-induced dopamine release in the striatum of intact and 6-hydroxydopamine-treated rats: differential effects of monoamine oxidase A and B inhibitors.

Administration of L-DOPA (50 mg/kg) elicits a significant increase in extracellular dopamine in striata of rats treated with the catecholaminergic neurotoxin 6-hydroxydopamine but not in striata of intact rats. To assess the role of dopaminergic nerve terminals in determining the effects of exogenous L-DOPA on extracellular dopamine levels in striatum, we examined the relative contributions of monoamine oxidase A and monoamine oxidase B to the catabolism of dopamine synthesized from exogenous L-DOPA. Extracellular concentrations of dopamine and its catabolite, 3,4-dihydroxyphenylacetic acid, were monitored with in vivo dialysis in striata of intact rats and of rats with unilateral 6-hydroxydopamine lesions of striatal dopamine. Clorgyline (2 mg/kg), an inhibitor of monoamine oxidase A, significantly increased dopamine and decreased 3,4-dihydroxyphenylacetic acid in intact but not in dopamine-depleted striata. Inhibition of monoamine oxidase B with either L-deprenyl (1 mg/kg) or Ro 19-6327 (1 mg/kg) did not significantly affect dopamine or 3,4-dihydroxyphenylacetic acid in striata of intact or dopamine-depleted rats. In intact rats, administration of clorgyline in conjunction with L-DOPA produced a > 20-fold increase in dopamine and prevented the L-DOPA-induced increase in 3,4-dihydroxyphenylacetic acid. Although both L-deprenyl and Ro 19-6327 administered in combination with L-DOPA elicited a small but significant increase in dopamine, levels of 3,4-dihydroxyphenylacetic acid were not affected. In rats pretreated with 6-hydroxydopamine, clorgyline had no significant effect on the increases in dopamine and 3,4-dihydroxyphenylacetic acid elicited by L-DOPA. Furthermore, neither L-deprenyl nor Ro 19-6327 affected L-DOPA-induced increases in dopamine and 3,4-dihydroxyphenylacetic acid in dopamine-depleted striata. The present findings indicate that deamination by monoamine oxidase A is the primary mechanism for catabolism of striatal dopamine, both under basal conditions and after administration of exogenous L-DOPA. Loss of dopaminergic terminals eliminates this action of monoamine oxidase A but does not enhance deamination by monoamine oxidase B. These data support a model in which exogenous L-DOPA elicits enhanced extracellular accumulation of dopamine in the dopamine-depleted striatum because some transmitter synthesis occurs at nondopaminergic sites and the dopamine terminals that normally take up and catabolize this pool of transmitter are absent.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Differential effect of systemic administration of bromocriptine and L-dopa on the release of acetylcholine from striatum of intact and 6-OHDA-treated rats.

A presumed balance between striatal dopaminergic and cholinergic systems forms a major theoretical framework for the development of new agents for the treatment of Parkinson's disease. We therefore studied the effect of two drugs currently used as anti-parkinsonian agents, bromocriptine (BROMO) and L-beta-3,4-dihydroxyphenylalanine (L-DOPA), on the release of striatal acetylcholine (ACh) in intact and 6-hydroxy-dopamine-treated rats using in vivo microdialysis. Lesioned rats with a > 90% tissue depletion of striatal dopamine (DA) had a significantly higher output of striatal ACh than unlesioned rats (88 fmol/min vs. 52 fmol/min; 0.3 mumol/l neostigmine in perfusate). BROMO (4 mg/kg) inhibited the output of striatal ACh in both groups. Whereas the lowest dose of L-DOPA (50 mg/kg) potently stimulated ACh output in lesioned rats, unlesioned rats were significantly less responsive. A higher dose of L-DOPA (100 mg/kg) stimulated ACh output to the same extent in both groups. At the highest dose tested, L-DOPA (200 mg/kg) given to intact rats did not further increase striatal ACh output. Thus, BROMO decreases whereas L-DOPA increases striatal ACh release after systemic application. Therapeutic as well as side effects of L-DOPA may therefore be mediated by neurochemical alterations that are more complex than previously thought.

Acetylcholine↗
PubMed1993

Presynaptic alterations associated with enhancement of evoked release and synthesis of norepinephrine in hippocampus of chronically cold-stressed rats.

We have previously demonstrated that prior exposure to chronic cold stress does not alter basal levels of norepinephrine (NE) release or synthesis in hippocampus of rat. However, in response to a subsequent novel stressor, an enhancement of both of these noradrenergic parameters is observed in the chronically stressed animals relative to naive controls. In the present experiments, we have examined whether the biochemical sensitization of NE release and synthesis produced by chronic stress can be demonstrated by local depolarization of the noradrenergic nerve terminals with elevated K+. The local application of elevated K+ in dorsal hippocampus resulted in a greater increase in extracellular NE and 3,4-dihydroxyphenylacetic acid (DOPAC) in chronically stressed rats than in naive controls. It is proposed that in dorsal hippocampus, extracellular NE and DOPAC provide measures of NE release and biosynthesis, respectively. Therefore, these data suggest that local depolarization, similar to novel stress, elicits both enhanced NE release and synthesis in chronically stressed rats. One factor that is known to modulate both of these processes is the presynaptic alpha-2 adrenergic receptor. Therefore, we examined whether a change in the sensitivity of these receptors might contribute to the altered noradrenergic responsivity observed in chronically stressed rats. Local administration of clonidine, an alpha-2 receptor agonist, produced a decrease in extracellular NE and DOPAC in both naive and chronically stressed rats. The dose-response curve for the effect of clonidine on NE was shifted to the left in the latter group. In addition, local administration of idazoxan, an alpha-2 receptor antagonist, produced a greater increase in extracellular NE and DOPAC in the chronically stressed rats than in naive controls.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

In vivo regulation of extracellular dopamine in the neostriatum: influence of impulse activity and local excitatory amino acids.

It has been suggested that dopamine release can be evoked by excitatory amino acids acting on dopaminergic terminals, as well as by the classical process of impulse-evoked exocytosis. We used in vivo microdialysis to examine whether endogenous excitatory amino acids locally evoked dopamine efflux under basal conditions. Infusion of N-methyl-d-aspartate (NMDA) or kainate into the neostriatum increased extracellular dopamine, and this effect was blocked by co-infusion of 2-amino-5-phosphonovalerate (APV) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), respectively. However, neither these antagonists nor kynurenate decreased extracellular dopamine when administered alone. In contrast, infusion of tetrodotoxin into the medial forebrain bundle reduced extracellular dopamine to below the limit of detection of our assay. These and other findings reviewed in this report suggest to us that extracellular dopamine in the neostriatum is not stimulated locally by endogenous excitatory amino acids.

2-Amino-5-phosphonovalerate↗
PubMed1993

Stress-induced dopamine release in the neostriatum: evaluation of the role of action potentials in nigrostriatal dopamine neurons or local initiation by endogenous excitatory amino acids.

It has been hypothesized that excitatory amino acids can initiate dopamine release in neostriatum. We examined whether the increase in extracellular dopamine in neostriatum produced by acute stress reflects presynaptic initiation of dopamine release by endogenous excitatory amino acids. Thirty minutes of intermittent tail-shock stress significantly elevated extracellular concentrations of dopamine, glutamate, aspartate, and gamma-aminobutyric acid in neostriatum of freely moving rats as measured with in vivo microdialysis. Local infusion of the N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonovalerate or the non-N-methyl-D-aspartate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione via the dialysis probe did not attenuate the stress-induced increase in extracellular dopamine. In fact, the increase was prolonged in rats treated with specific excitatory amino acid receptor antagonists. Infusion of tetrodotoxin into medial forebrain bundle increased extracellular glutamate and aspartate in neostriatum yet reduced basal dopamine in extracellular fluid to below the limit of detection of the assay and eliminated the stress-induced increase in extracellular dopamine. These findings fail to support the hypothesis that the stress-induced increase in extracellular dopamine in neostriatum is initiated locally by excitatory amino acids. Rather, the effects of stress on extracellular dopamine seem to be determined by impulse propagation in dopamine neurons.

2-Amino-5-phosphonovalerate↗
PubMed1993

Impact of L-dopa on striatal acetylcholine release: effects of 6-hydroxydopamine.

We investigated the effects of the dopamine (DA) precursor L-dihydroxyphenylalanine (L-DOPA) on electrically evoked acetylcholine (ACh) overflow from rat striatal slices. Some animals were pretreated 1 to 2 months earlier with 6-hydroxydopamine, (6-OHDA), a catecholamine neurotoxin, so as to selectively destroy DA terminals (98.6% striatal DA depletion). Although the addition of L-DOPA (10 microM) produced a 37% inhibition of ACh overflow in slices from lesioned rats, it failed to affect ACh overflow in slices from intact animals. In contrast, ACh overflow from intact slices exposed to L-DOPA and to the DA uptake inhibitor nomifensine (1 microM) was 22% greater than in the presence of nomifensine without L-DOPA. ACh overflow from slices prepared from lesioned rats was 45% greater with both drugs than in the presence of nomifensine by itself. Superfusion with the aromatic L-amino acid decarboxylase (AADC) inhibitor NSD-1055 (250 microM) abolished the inhibitory effects of L-DOPA, as did L-sulpiride (1 microM), an inhibitor of DA receptors of the D2 subtype. These results suggest that inhibition of ACh overflow by L-DOPA is mediated by DA formed from exogenous L-DOPA which then acts on D2 receptors. They further indicate that the net impact of the loss of nigrostriatal terminals is an increased dopaminergic inhibition of striatal cholinergic interneurons in response to exogenous L-DOPA. This appears to result in large part from a lesion-induced reduction in high-affinity reuptake of DA formed from exogenous L-DOPA.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Electrophysiological, biochemical, and behavioral studies of acute haloperidol-induced depolarization block of nigral dopamine neurons.

The electrophysiological, biochemical and behavioral responses produced by administration of haloperidol were studied in intact rats and in rats with 6-hydroxydopamine-induced partial lesions of the nigrostriatal dopamine pathway. In both control rats and rates tested four to 10 days postlesion, the electrophysiological response of nigral dopamine neurons to increasing doses of haloperidol consisted of either: (1) an increase in firing rate which reached a plateau at six to 10 spikes per second, or (2) no response (i.e., less than 20% change in firing rate). Administration of additional doses of haloperidol up to lethal levels did not elicit further changes in dopamine cell firing in these rats. In contrast, in 6-hydroxydopamine-treated rats tested four to six weeks postlesion, acute administration of haloperidol was not only more consistent in producing increases in dopamine cell firing rate, but also caused six out of seven dopamine neurons tested to cease firing upon entering a state of depolarization block. In all cases in which depolarization block was observed, dopamine cell firing was reinstated by either iontophoretic application of gamma-aminobutyric acid or intravenous administration of apomorphine. In parallel studies, haloperidol caused an increase in the extracellular dopamine levels measured by microdialysis in the striatum of control rats, whereas administration of the same dose of haloperidol to 6-hydroxydopamine-treated rats four to six weeks postlesion did not elicit any change in extracellular dopamine levels. In addition, administration of haloperidol at a dose which was ineffective in control rats produced gross motor deficits in the 6-hydroxydopamine-treated rats when tested four to six weeks postlesion. These results show that 6-hydroxydopamine-induced dopamine depletions produce a time-dependent change in the responsivity of the nigrostriatal dopamine system to acute haloperidol administration. In this altered system, the induction of depolarization block of spike activity in nigral dopamine neurons by haloperidol was not associated with a corresponding decrease in extracellular dopamine levels measured in the striatum. However, it appeared that depolarization block did prevent haloperidol-induced increases in extracellular dopamine levels. The occurrence of depolarization block in the dopamine-depleted animal may limit the capacity of this system to respond to additional compromise, in spite of the compensatory processes that contribute to maintaining motor function.

Animals↗
PubMed1992

Extracellular dopamine in striatum: influence of nerve impulse activity in medial forebrain bundle and local glutamatergic input.

Microdialysis probes were used to measure dopamine in, and to administer glutamate receptor antagonists and agonists to, the striatum of unanesthetized rats. Antagonists used were: kynurenate, 2-amino-5-phosphonovalerate and 6-cyano-7-nitroquinoxaline-2,3-dione. Agonists used were: N-methyl-D-aspartate and kainate. In some rats an additional dialysis probe was implanted in medial forebrain bundle for infusion of tetrodotoxin (10 microM) to block action potential propagation along dopaminergic axons in this pathway. The latter treatment reduced dopamine in striatal dialysate to below detectable levels (less than 0.5 pg). The quantity of dopamine in striatal dialysate was not reduced by the local application of glutamate receptor antagonists. At lower concentrations, the receptor antagonists failed to alter significantly the quantity of dopamine, whereas the highest concentration of each antagonist increased the amount of dopamine in the dialysate. At the highest concentration tested (0.75 mM or 1.0 mM), as well as at a lower concentration (0.1 mM), 2-amino-5-phosphonovalerate and 6-cyano-7-nitroquinoxaline-2,3-dione blocked the dopamine-releasing effects of exogenously applied N-methyl-D-aspartate (1.0 mM) or kainate (0.1 mM), respectively. Thus, concentrations of glutamate receptor antagonists that produced effective pharmacological blockade of the respective receptors had no effect on the basal amount of dopamine in striatal extracellular fluid. Finally, N-methyl-D-aspartate and kainate produced a significant elevation in extracellular dopamine during the infusion of tetrodotoxin into the medial forebrain bundle, indicating that impulse activity in this pathway is not necessary for dopamine release produced by glutamate receptor agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1992

Enhanced tyrosine hydroxylation in hippocampus of chronically stressed rats upon exposure to a novel stressor.

We have used microdialysis to measure the in vivo level of tyrosine hydroxylation in hippocampus of the freely moving rat. An inhibitor of aromatic amino acid decarboxylase, NSD-1015, was administered through the dialysis probe and the resulting accumulation of 3,4-dihydroxyphenylalanine (DOPA) in extracellular fluid of hippocampus was quantified. Administration of the tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine, decreased extracellular DOPA to undetectable level. In addition, both systemic and local application of clonidine, an alpha 2-adrenergic agonist, produced a decrease in extracellular DOPA. In response to acute tail shock, a significant increase in extracellular DOPA was observed. Thus, it appears that in vivo accumulation of DOPA after local administration of NSD-1015 provides a reliable index of hippocampal tyrosine hydroxylation. We have used this technique to investigate whether prior exposure to chronic stress alters the in vivo level of tyrosine hydroxylation in hippocampus under basal conditions as well as in response to a novel stressor. In rats previously exposed to chronic cold stress, the basal accumulation of extracellular DOPA did not differ from naive controls. Acute tail shock, however, produced a significantly greater and more prolonged elevation in extracellular DOPA of chronically stressed rats. These data suggest that enhanced biosynthetic capacity of noradrenergic terminals may be one mechanism underlying adaptation to chronic stress.

Animals↗
PubMed1992

In vivo neurochemical evaluation of striatal serotonergic hyperinnervation in rats depleted of dopamine at infancy.

Destruction of nigrostriatal dopamine (DA) neurons with 6-hydroxydopamine (6-OHDA) early in development results in hyperinnervation of striatum by the serotonergic afferents deriving from the dorsal raphe nucleus. We have used in vivo microdialysis to investigate the degree to which serotonergic neurotransmission in striatum is altered by this increase in the density of serotonin (5-HT) terminals. The effects of several manipulations known to influence 5-HT function on extracellular 5-HT and 5-hydroxyindoleacetic acid in striatum were compared in adult rats treated neonatally with 6-OHDA and in intact adult rats. Basal levels of 5-HT in extracellular fluid (ECF) of striatum were similar in neonatally DA-depleted rats and in intact rats. Perfusion with the 5-HT reuptake blocker, fluoxetine (100 microM), increased 5-HT in striatal ECF of neonatally DA-depleted rats to levels that were threefold greater than those achieved in intact rats. Likewise, K(+)-depolarization of the 5-HT terminals (100 mM in perfusate) or systemic administration of the 5-HT releaser, (+/-)-fenfluramine (10 mg/kg i.p.), increased the concentration of 5-HT in striatal ECF of neonatally DA-depleted rats to levels approximately threefold greater than those observed in striatum of intact rats. These findings indicate that the 5-HT hyperinnervation of striatum that takes place in rats depleted of DA at infancy is associated with an increased capacity for neurotransmitter release in this system. Concomitant increased in high-affinity 5-HT uptake may prevent the occurrence of any measurable changes in the resting concentration of 5-HT in striatal ECF.

Animals↗
PubMed1991

Single-unit and physiological analyses of brain norepinephrine function in behaving animals.

In behaving cats, the single-unit activity of locus coeruleus noradrenergic neurons is strongly activated by a variety of challenges (stressors). For example, exposing cats to a dog or to loud white noise, dramatically increases the activity of these neurons and simultaneously produces strong activation of the sympathetic nervous system. Similarly, glucoregulatory, thermoregulatory, and cardiovascular challenges also coactivate noradrenergic neurons and the sympathetic nervous system. A related research program utilized a simple brainstem response (the monosynaptic jaw closure reflex) to explore the physiological significance of this response of brain noradrenergic neurons. Conditions which activate these neurons were also shown to potentiate the elicited jaw closure-reflex response. Importantly, when the noradrenergic input to the motor side of this reflex pathway was destroyed with a neurotoxin, the conditions which previously potentiated the reflex were now ineffective. These data represent the first demonstration that the release of norepinephrine, at a specific site, and under physiological conditions, facilitates behavioral output in the intact organism.

Action Potentials↗
PubMed1991

Prior exposure to chronic stress results in enhanced synthesis and release of hippocampal norepinephrine in response to a novel stressor.

The release and synthesis of norepinephrine (NE) in hippocampus were measured in naive and chronically cold-stressed rats in response to acute tail-shock stress. Using in vivo microdialysis, it was determined that the basal extracellular concentrations of NE and 3,4-dihydroxyphenylacetic acid (DOPAC) in hippocampus were the same in the two groups. However, 30 min of intermittent tail shock produced a greater elevation of extracellular NE and 3,4-dihydroxyphenylacetic acid in the chronically cold-stressed rats than in the native controls. In hippocampus, the extracellular concentration of DOPAC may reflect NE biosynthesis, and thus the enhanced DOPAC response in the chronically stressed rats suggests an increase in NE synthesis. In order to investigate this possibility, two further methods of assessing NE biosynthesis were employed. Tyrosine hydroxylase (TH) activity was assayed in vitro in the presence of saturating concentrations of cofactor. No change in maximal TH activity could be detected in hippocampus of chronically cold-stressed rats. In addition, the in vivo rate of tyrosine hydroxylation in cold-stressed rats was measured by the accumulation of 3,4-dihydroxyphenylalanine in tissue following inhibition of aromatic amino acid decarboxylase. It was found that, whereas basal synthesis was the same in both groups of rats, synthesis accompanying a novel stressor was increased to a greater extent in the chronically stressed rats.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Environmental stress increases extracellular dopamine in striatum of 6-hydroxydopamine-treated rats: in vivo microdialysis studies.

Bilateral intraventricular injections of 6-hydroxydopamine depleted dopamine (DA) in striatal tissue of rats by 88%. Tail shock increased DA in striatal extracellular fluid of these rats from 10 to 17 pg/20 microliters as measured by microdialysis, values less than half those seen in normal striatum. The increase was observed even in rats that were akinetic. DA in extracellular fluid after stress was negatively correlated with behavioral performance. Thus, residual nigrostriatal DA neurons are responsive to stress but do not produce normal DA levels in striatal extracellular fluid.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Effects of L-dopa on extracellular dopamine in striatum of normal and 6-hydroxydopamine-treated rats.

In vivo microdialysis was used to examine the effect of L-3,4-dihydroxyphenylalanine (L-DOPA) administration upon dopamine (DA) in extracellular fluid both in intact striatum and in striatum of rats treated with the catecholaminergic neurotoxin 6-hydroxydopamine (6-HDA). Basal extracellular levels of DA were not significantly altered by 6-HDA unless the DA content of striatal tissue was reduced to less than 20% of control. Peripheral aromatic amino acid decarboxylase (AADC) inhibition (RO4-4602, 50 mg/kg i.p.) followed by L-DOPA treatment (100 mg/kg i.p.) elevated extracellular DA in striatum of control rats from 37 +/- 5 to 68 +/- 11 pg/sample (n = 7; values corrected for recovery of the dialysis probe). In animals with severe bilateral depletions of DA in striatal tissue (mean depletion 87%; n = 6), L-DOPA increased extracellular DA in striatum from 8 +/- 3 to 266 +/- 60 pg/sample. In animals with large unilateral depletions of DA in striatal tissue (mean depletion 96%; n = 6), the increase in extracellular DA in striatum after L-DOPA was greater on the lesion side (from 7 +/- 4 to 245 +/- 67 pg/sample) than on the intact side (from 28 +/- 11 to 61 +/- 8 pg/sample). Animals with unilateral DA depletions showed contralateral circling behavior after L-DOPA. Increases in extracellular DA approaching the magnitude of those occurring in DA-depleted striata were observed when intact animals were treated with nomifensine (5 mg/kg i.p.; n = 5), an inhibitor of high-affinity DA uptake, in addition to L-DOPA.

Animals↗
PubMed1990

Partial damage to nigrostriatal bundle: compensatory changes and the action of L-dopa.

Parkinson's disease is associated with degeneration of the nigrostriatal bundle. However, the neurological symptoms that accompany this disease do not emerge until the degenerative process is almost complete. Early studies with animals models suggested that the extensive preclinical phase of Parkinsonism was due in part to the development of a compensatory hyperactivity within remaining dopamine-containing neurons. Other studies suggested that systemic administration of L-DOPA could reduce the neurological symptoms once they emerged by further increasing the availability of dopamine in striatum. Subsequent work has supported both hypothesis.

Animals↗