Effects Of Unilateral 6-hydroxydopamine Lesions Research Articles

A unilateral 6-hydroxydopamine lesion decreases the expression of metabotropic glutamate receptors in rat substantia nigra

Loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) in Parkinson's disease (PD) leads to augmentation of glutamatergic activity in the subthalamic nucleus (STN). Moreover, antagonizing excitotoxicity has yielded mostly symptomatic improvements in experimental animals of PD. Therefore, we used immunocytochemistry to examine the effect of unilateral 6-hydroxydopamine lesions of SNc on the expression of metabotropic glutamate receptors (mGluR1a, 2/3, 5, 4, 8) and tyrosine hydroxylase (TH). 6-Hydroxydopamine causes a fall in the number of mGluRs and TH in the lesioned lateral substantia nigra. Pharmacological activation of group II or III mGluRs or blockade of group I mGluRs for 1 week significantly increased the expression of the same group receptors. The alteration in the receptor expression may be a compensatory mechanism developed after mGluRs ligands neuroprotective treatment.

A unilateral 6-hydroxydopamine lesion decreases the expression of metabotropic glutamate receptors in rat substantia nigra

Loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) in Parkinson's disease (PD) leads to augmentation of glutamatergic activity in the subthalamic nucleus (STN). Moreover, antagonizing excitotoxicity has yielded mostly symptomatic improvements in experimental animals of PD. Therefore, we used immunocytochemistry to examine the effect of unilateral 6-hydroxydopamine lesions of SNc on the expression of metabotropic glutamate receptors (mGluR1a, 2/3, 5, 4, 8) and tyrosine hydroxylase (TH). 6-Hydroxydopamine causes a fall in the number of mGluRs and TH in the lesioned lateral substantia nigra. Pharmacological activation of group II or III mGluRs or blockade of group I mGluRs for 1 week significantly increased the expression of the same group receptors. The alteration in the receptor expression may be a compensatory mechanism developed after mGluRs ligands neuroprotective treatment.

Effect of unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway on GABA A receptor subunit gene expression in the rodent basal ganglia and thalamus

In Parkinson's disease, changes in GABAergic activity occurring downstream of the striatal dopamine loss are accompanied by reciprocal changes in GABA A receptor binding, the underlying molecular mechanisms for which are unknown. This study examined whether changes in expression of the genes encoding known GABA A receptor subunits (α 1–4, β 1–3, γ 1–3 and δ) could account for this receptor plasticity using a rodent model of Parkinson's disease with a 6-hydroxydopamine-induced nigrostriatal lesion. Analysis of autoradiograms of the basal ganglia and thalamus revealed changes in expression of only four of the 11 subunits studied. Expression of α 1 and β 2 subunit genes was altered in a parallel manner following a 6-hydroxydopamine lesion; messenger RNA levels for both were significantly increased in the substantia nigra pars reticulata (11±4% and 17±1%, respectively), and significantly reduced in the globus pallidus (18±3% and 16±3%, respectively) and parafascicular nucleus (19±3% and 16±5%, respectively). Smaller changes in the messenger RNA levels encoding the α 1 subunit in the lateral amygdala (8±1% decrease) and the α 4 and γ 2 subunits in the striatum (10±2% and 6±1% increase, respectively) were also observed. No changes in expression were noted for any other subunits in any region studied. Clearly, both region- and subunit-specific regulation of GABA A receptor subunit gene expression occurs following a nigrostriatal tract lesion. The changes in expression of the α 1 and β 2 subunit genes probably contribute to the documented changes in GABA A receptor binding following striatal dopamine depletion. Moreover, they provide a molecular basis by which the pathological changes in GABAergic activity in Parkinson's disease may be partially compensated.

Recovery after nigral grafting in 6-hydroxydopamine lesioned rats is due to graft function and not significantly influenced by the remaining ipsilateral or contralateral host dopaminergic system

The aim of this study was to evaluate whether the recovery observed after grafting of fetal nigral cells in 6-hydroxydopamine lesioned rats is due to the graft itself, and whether the participation of the remaining host dopaminergic system is necessary. The effects of unilateral 6-hydroxydopamine lesion on rotational behavior were not significantly affected by sham grafting or by sham grafting plus repeat ipsilateral lesion, but were suppressed by nigral grafting, and by contralateral lesion. Immunohistochemical and in situ hybridization study of right striata of rats subjected to right-side lesion then right-side sham-grafting, and of right and left striata from rats subjected to right-side lesion then right-side sham-grafting then repeat right-side lesion then left-side lesion, revealed (a) no significant amphetamine-induced Fos activation, (b) marked increases in preproenkephalin mRNA levels, and (c) decreases in preprotachykinin levels, with no significant differences in any of these variables among these three types of striata. After nigral grafting, however, intense Fos expression was observed in the striatum, and preproenkephalin and preproenkephalin mRNA levels returned to normal. This recovery was maintained after subsequent repeat ipsilateral 6-hydroxydopamine lesion followed by contralateral lesion. The results demonstrate that, after dopaminergic denervation, the nigral graft itself is able to induce recovery in the assessed parameters, and that these effects of grafting into striata with maximal unilateral 6-hydroxydopamine lesion are due to graft function, and are not significantly influenced by the remaining ipsilateral or contralateral host dopaminergic system. Additionally, it is interesting to note that bilateral denervation led to changes in striatal preproenkephalin and preproenkephalin mRNA levels similar to those observed after unilateral lesion.

Drug-free evaluation of rat models of parkinsonism and nigral grafts using a new automated rotarod test

A variety of tests are available for the evaluation of behavioural deficits in rat models of hemiparkinsonism; many, however, are of limited applicability or insufficiently objective. The drug-induced turning behaviour test is widely used. A disadvantage of this test is that the use of drugs may lead to misleading results. Here, we describe a drug-free rotarod test that was used to evaluate the effects of unilateral 6-hydroxydopamine lesions, nigral grafts, and subrotational doses of apomorphine. The rotarod unit was automated and interfaced to a personal computer allowing automatic recording of the time that each rat was able to stay on the rod at different rotational speeds (i.e., progressively increasing the difficulty of the task). A combination of lesion-induced deficits resembling those of Parkinson's disease appears to be involved in falling from the rod. The test shows high effectiveness for identifying rats with maximal dopaminergic lesions, but is also effective for identifying partial lesions. Rotarod performance profiles were useful for investigating the effects of intrastriatal nigral grafts, since low rotation speeds revealed differences from lesioned rats (i.e., improvements) while higher speeds revealed differences from normal rats (i.e., remaining deficits and partial lesions). The test was effective regardless of whether rats were trained on the rod before lesion, after lesion, or after grafting. Injections of apomorphine (0.0125 and 0.0250 mg/kg) did not induce consistent improvements. These results indicate that the rotarod test is a useful drug-free procedure for overall evaluation of basic motor abilities in rat models of parkinsonism and treatment-induced changes.

Pretreatment With Neurokinin Substance P But Not With Cholecystokinin-8S Can Alleviate Functional Deficits of Partial Nigrostriatal 6-Hydroxydopamine Lesion

Nikolaus, S., J. P. Huston, B. KÖRber, C. Thiel and R. K. W. Schwarting. Pretreatment with neurokinin substance P but not with cholecystokinin-8S can alleviate functional deficits of partial nigrostriatal 6-hydroxydopamine lesion. Peptides 18(8) 1161–1168, 1997.—The neuropeptide substance P (SP) has been implicated in the control of various neuro-behavioral functions including reinforcement and learning processes. It also exerts neurotrophic and regenerating effects in vitro and in vivo. A previous study indicated a potential therapeutic effect of SP in rats with partial 6-hydroxydopamine lesions of the nigrostriatal dopamine system when SP was administered after the lesion. The purpose of the present study was to determine whether prelesion treatment with SP would also interact with the effects of unilateral 6-hydroxydopamine lesion of the substantia nigra. Thus, SP (50 μg/kg) was administered i.p. on 8 consecutive days prior to unilateral lesion of the substantia nigra. Furthermore, we investigated the effects of prelesion treatment with cholecystokinin-8S (CCK; 1 μg/kg), another neuropeptide, which is closely related to dopaminergic neurons, and which also can have neurotrophic and neuroprotective functions. Our results show that animals with partial neostriatal dopamine depletions (residual dopamine levels of more than 10%) did not show turning asymmetries when pretreated with SP, whereas animals pretreated with vehicle exhibited an initial ipsiversive asymmetry from which they recovered. In contrast, behavioral asymmetries were most pronounced in animals which had been pretreated with CCK. These peptide treatments did not affect the degree of neostriatal dopamine depletion; however, dihydroxyphenylacetic acid/dopamine ratios were enhanced in the neurostriatum of animals with partial dopamine damage after SP- and CCK-pretreatment, and in the ventral striatum of SP-pretreated animals. These data provide evidence that prelesion treatment with SP, but not with CCK, can alleviate functional deficits induced by a partial nigro-striatal dopamine lesion. This effect may be related to enhanced ventral striatal dopamine activity and/or to the peptide’s known effects on learning, motivation, and emotion.

Effects of unilateral 6-hydroxydopamine lesions on neuropeptide immunoreactivity in the basal ganglia of the common marmoset, Callithrix jacchus, a quantitative immunohistochemical analysis

Previous immunocytochemical studies in rats have indicated that striatal dopamine depletion leads to an increase in enkephalin-immunoreactivity and a decrease in substance P-immunoreactivity in the striatum. Similar studies in primates have lead to contradictory results. In the present study changes in tyrosine hydroxylase-, met-enkephalin- and substance P-immunoreactivity were determined in the basal ganglia of 6 common marmosets Callithrix jacchus following dopamine depletion by unilateral intracerebral 6-hydroxydopamine (6-OHDA) injections using three different survival times. The non-lesioned side served as an intra-individual control. Tyrosine hydroxylase immunoreactivity was strongly reduced in the entire ipsilateral striatum. Enkephalin-immunoreactivity was increased throughout the striatum. Substance P-immunoreactivity was significantly increased in only one case in the caudate nucleus and in two cases in the putamen, while in other cases either a non-significant increase or decrease was found. Therefore, the results of the present study indicate that in marmosets dopamine has a inhibiting effect on the levels of striatal enkephalin, while its effect on substance P (SP) appears to be absent.

Differential effects of dopamine depletion on the binding and mRNA levels of dopamine receptors in the shell and core of the rat nucleus accumbens

In the present study, using quantitative receptor autoradiography and in situ hybridization histochemistry the effects of unilateral 6-hydroxydopamine lesions on the binding density levels of dopamine D 1 and D 2 receptors and the levels of mRNA encoding D 1 and D 2 receptors were investigated in the core and shell territories of the nucleus accumbens (Acb) and in the caudate-putamen (CP). The lesions induced contrasting effects on the D 1 binding and D 1 mRNA in the Acb and CP, i.e. an increase in binding and a decrease in the mRNA levels. For the D 2 receptor an increase in both the binding density and mRNA levels was observed. The lesion-induced effects displayed regional differences. For D 1 mRNA and D 1 and D 2 binding, the lesion effect was more pronounced in the core than in the shell of the Acb. For the D 2 mRNA levels an increase was observed in the CP but not in the two territories of the Acb. Furthermore, the decrease in D 1 mRNA was greater in the rostral than in the caudal parts of the core and shell of the Acb. These results indicate that the core and shell of the Acb and the CP respond differentially to dopamine depletion.

Striatal G-proteins: Effects of unilateral 6-hydroxydopamine lesions

To investigate the molecular mechanisms of denervation-induced dopamine receptor supersensitivity, levels of striatal G-proteins were examined in 6-hydroxydopamine (6-OHDA)-lesioned rats. Increased levels of the α-subunits of G s and G olf, as measured by immunoblotting, were observed 8 days postlesion and remained elevated up to day 28 (25–45% over the time course). G i levels were significantly increased only on day 8 (20%) and G o levels remained unaltered. These results suggest that stimulatory G-proteins may be involved in the long-term maintenance of dopamine receptor supersensitivity following denervation.

Long-term changes in striatal opioid systems after 6-hydroxydopamine lesion of rat substantia nigra

The effects of unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway on striatal opioid peptides and receptors were determined at different time-intervals, from three days up to 24 weeks, post-lesion. Mu, delta and kappa opioid binding site densities in the ipsilateral caudate-putamen were decreased by 25–50% in rats which exhibited a greater than 90% loss of dopamine uptake sites. Differentiation of radioligand binding to kappa 1 and kappa 2 subtypes demonstrated a selective loss of kappa 2 sites post-lesion. The onset of significant 6-hydroxydopamine lesion-induced changes in striatal opioid binding sites was delayed with respect to the loss of dopamine uptake sites. Furthermore, maximal loss of dopamine uptake sites was apparent within seven days post-lesion, but not until two to four weeks for mu, delta and kappa sites. In animals which exhibited an incomplete loss of dopamine uptake sites (less than 80%) there was no significant change in opioid binding site density. Striatal proenkephalin and prodynorphin messenger RNA levels were increased and decreased, respectively, after complete 6-hydroxydopamine lesion. Modulation of peptide messenger RNA levels was apparent within seven days and was maintained up to 24 weeks post-lesion. In contrast, proenkephalin and prodynorphin messenger RNA levels were unchanged in animals which exhibited an incomplete loss of striatal dopamine uptake sites. Taken together, these observations suggest that the majority of mu, delta and kappa 2 opioid binding sites are localized on non-dopaminergic elements in the caudate-putamen, but that substantia nigra innervation plays a role in the control of striatal opioid receptor expression. The 6-hydroxydopamine lesion-induced decreases in striatal opioid binding site density may, in part, be a function of agonist-induced receptor downregulation. Alternatively, both opioid receptor and peptide expression in the caudate-putamen may be directly, but independently, regulated by ventral mesencephalic neurons.

Autoradiographic identification of D 1 dopamine receptors labelled with [ 3H]dopamine: Distribution, regulation and relationship to coupling

On the basis of experiments made on striatal membranes, Leff and Creese [ Molec. Pharmac. (1985) 27, 184–192] have proposed that tritiated dopamine binds to a high-affinity agonist state of D 1 dopamine receptors (D 1h) which adopt this conformation when they are associated with the GTP-binding protein involved in the transduction process. Quantitative autoradiography was thus used to look for the distribution of these D 1h sites in the rat brain and to compare it with that of D 1 receptors labelled with [ 3H]7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine ([ 3H]SCH23390), a D 1 antagonist. The effects of unilateral 6-hydroxydopamine lesion of the ascending dopamine pathways on the density of [ 3H]dopamine D 1h and [ 3H]SCH23390 binding sites in the striatum and the nucleus accumbens were also analysed. In the striatum, when D 2 receptors were blocked by spiroperidol (20 nM), [ 3H]dopamine was found to bind specifically to dopamine receptors of the D 1 type. Complementary experiments made with dopamine uptake blockers indicated that high-affinity dopamine uptake sites were not labelled by [ 3H]dopamine under our experimental conditions. The anatomical distribution of [ 3H]dopamine D 1h binding sites was found to be markedly different from that of [ 3H]SCH23390 binding sites. This was particularly the case in the substantia nigra, some amygdaloid nuclei and the prefrontal cortex—structures in which the ratios between [ 3H]SCH23390 and [ 3H]dopamine binding sites were more than seven-fold higher than that observed in the striatum. [ 3H]SCH23390 binding was not significantly affected in either the striatum or the nucleus accumbens six weeks after a complete unilateral destruction of ascending dopamine pathways. In contrast, a marked decrease in [ 3H]dopamine D 1h binding sites was found in both structures, but this effect was lower in the medioventral (−60%) than in the laterodorsal (− 81%) part of the striatum, even though dopamine denervation was uniform throughout the structure. Preincubation of the sections with dopamine (0.5 μ M) led to a partial recovery (+ 126%) in the lesioned striatum and an increase of [ 3H]dopamine labelling in the control striatum (+68%). This suggests that the presence of dopamine stabilizes the D 1h state of D 1 receptors. The absence or low amounts of dopamine, either due to dopamine denervation or naturally occurring (prefrontal cortex), would then impair the [ 3H]dopamine D 1h binding. In addition, a lower coupling of D 1 receptors with adenylate cyclase was observed in the substantia nigra when compared to that in the striatum: this may explain the relatively weak [ 3H]dopamine binding in the substantia nigra. Similarly, the lower loss of [ 3H]dopamine binding sites seen specifically in the medioventral part of the striatum in the 6-hydroxydopamine-lesioned rats could be related to a supersensitive dopamine-stimulated adenylate cyclase activity found in this striatal area [Herve´ et al. (1989) J. Neurosci. 9, 3699–3707], In conclusion, the D 1h state of the D 1 receptors is dependent on the endogenous dopamine levels and on the intensity of the D 1 receptor coupling. In order to explain both influences, it is proposed that the D 1h binding sites observed in brain sections are generated by the dissociation of a ternary complex in which dopamine, D 1 receptor and GTP-binding protein are associated.

A rostrocaudal gradient in the synthesis of enkephalin in nucleus accumbens.

A subpopulation of projection neurons in the nucleus accumbens uses the neuropeptide enkephalin as a neurotransmitter. The synthesis of enkephalin in striatal neurons is regulated by dopaminergic inputs. In the present study quantitative in situ hybridization histochemistry was used to examine the effects of unilateral 6-hydroxydopamine lesions of the ascending dopaminergic fibres on levels of enkephalin mRNA in subregions of the nucleus accumbens. It was found that the levels of enkephalin mRNA were increased throughout the nucleus after the lesion. However, the increase appeared to be much higher in rostral parts of the nucleus than in caudal parts, indicating regional differences in the effects of blockade of the dopaminergic neurotransmission. Possible causative factors for these differences are discussed.

Neuronal damage in the striatum following forebrain ischemia: lack of effect of selective lesions of mesostriatal dopamine neurons

Transient periods of global cerebral ischemia lead to selective neuronal damage in the striatum. We investigated the effects of unilateral 6-hydroxydopamine lesions of the mesostriatal dopamine (DA) system on the density and distribution of neuronal necrosis in the rat striatum following ischemia induced by bilateral occlusion of the common carotid arteries combined with hypotension. After both 12 and 15 min of ischemia, which caused slight and extensive striatal damage, respectively, there was no difference in the density of neuronal necrosis in the striatum between DA-lesioned and sham-operated animals. We conclude that the DA system alone does not modulate injury following complete cerebral ischemia, but may contribute significantly to damage following conditions such as during hypoglycemia and incomplete cerebral ischemia.

Nigral dopamine autoreceptors are exclusively of the D 2 type: Quantitative autoradiography of [ 125I]iodosulpride and [ 125I]SCH 23982 in adjacent brain sections

The effect of unilateral 6-hydroxydopamine lesions of the medial forebrain bundle on the specific binding of [ 125I]iodosulpride and [ 125I]SCH 23982 in the rat substantia nigra was determined by quantitative autoradiography of adjacent sections. The specific binding of [ 125l]iodosulpride was reduced by 40–70% on the lesioned side in the substantia nigra pars compacta, reticulata, lateralis and in the ventral tegmental area. In contrast, the specific [ 125I]SCH 23982 binding was unchanged in all subdivisions of the substantia nigra. The results indicate that dopamine autoreceptors are present in the substantia nigra and in the ventral tegmental area and that they are exclusively of the D 2 type.

Conditioned circling in rats: Bilateral involvement of the mesotelencephalic dopamine system demonstrated following unilateral 6-hydroxydopamine lesions

High rates of conditioned circling have previously been associated with a bilateral augmentation of striatal dopamine metabolism. These results suggest that both striata subserve this response. The present experiment further assessed this possibility by determining the effects of unilateral 6-hydroxydopamine lesions of the mesotelencephalic dopamine system on conditioned circling. Rats were initially trained to circle in their preferred direction for water reinforcement. Upon establishment of this response, they received unilateral lesions at the level of the lateral hypothalamus either contralateral or ipsilateral to the reinforced direction of circling. Reinforced responding was virtually abolished in rats with contralateral lesions. In contrast, rats lesioned ipsilateral to the direction of reinforced circling exhibited only a 50% decrease in rate of reinforced responding. Non-reinforced responding was increased only in rats with contralaterally placed lesions. Following 5 postoperative test sessions, the experimental contingencies were reversed. ‘Ipsilaterally lesioned’ rats were now required to circle away from their lesion whereas ‘contralaterally lesioned’ rats had to turn towards their lesion. The ‘Contralateral’ group acquired the reversal, such that reinforced responding occurred more frequently than non-reinforced responding. However, reinforced rates of responding did not reach preoperative rates. Conversely, ‘ipsilaterally lesioned’ rats could not learn to turn contraversively and now made more non-reinforced than reinforced responses. These findings suggest that conditioned circling is mediated by a bilateral involvement of the mesotelencephalic dopaminergic systems. However, the specific role of each side appears to be dependent upon its relationship with the direction of circling emitted.

Mesencephalic dopamine neurons regulate the expression of neuropeptide mRNAs in the rat forebrain.

We used in situ hybridization histochemistry with synthetic oligodeoxyribonucleotide probes to identify cells that synthesize mRNAs encoding tyrosine hydroxylase in the mesencephalon and substance P, enkephalin, and dynorphin in the rat forebrain. Dopaminergic cells in the mesencephalon project to the forebrain and influence neuropeptide levels. We examined the effect of unilateral 6-hydroxydopamine lesions (which eliminated tyrosine hydroxylase mRNA-containing cells in the mesencephalon) on substance P, enkephalin, and dynorphin mRNA levels. Substance P mRNA levels were depressed, whereas enkephalin mRNA levels were elevated in consecutive sections from striatal areas in all animals. The effects of the lesions on dynorphin mRNA levels were less robust, and considerable variation between animals was observed. Changes were evident in the levels of message in individual cells but not in the numbers of labeled cells. These effects were not uniform throughout the dopamine-innervated areas, suggesting degrees of control not apparent with RNA blot-hybridization or dot-blot analyses.

An examination of parkinsonian versus anhedonia contributions to self-stimulation impairments induced by dopamine dysfunction

Interference with brain dopamine neurotransmission can severely impair brain stimulation reward behavior. The significance of this impairment in reward behavior, however, has been a problematic issue. That is, it has been difficult to determine whether the dopamine dysfunction has attenuated the reward effect of the stimulation or has merely rendered the animal less able to generate the behavior required to obtain reinforcement. To experimentally re-assess this issue, the present studies examine the effect of unilateral 6-hydroxydopamine lesions of forebrain dopamine neurons on brain stimulation reward in animals. In general, these studies highlight the substantial motoric deficits produced by the lesion treatments. By combining lesion and neuroleptic drug treatments, however, it appeared that effects on reward could be detected.

Acute ipsilateral hyperalgesia and chronic contralateral hypoalgesia after unilateral 6-hydroxydopamine lesions of the substantia nigra

The effect of unilateral 6-hydroxydopamine lesions on flinch-jump thresholds to footshock was investigated during 3 months postoperative in rats. Preoperatively, the ipsilateral-contralateral thresholds were closely matched but postoperatively the flinch-jump thresholds to footshock applied to the body surface contralateral to the lesion hemisphere increased, whereas ipsilateral thresholds decreased. The ipsilateral decrease in threshold was maximal at postoperative day 1 but the contralateral increase persisted throughout testing. In control rats no ipsilateral-contralateral differences in the threshold were obtained. In both the control and 6-hydroxydopamine-treated groups there was an additional bilateral decline in jump threshold during the course of the experiment. These results suggest a role for dopaminergic and nondopaminergic participation in an animal's response to nociceptive stimulation.

Unilateral substantia nigra lesions and schedule-induced polydipsia

The present experiment investigated the effects of unilateral 6-hydroxydopamine lesions of the substantia nigra (SN) on schedule-induced polydipsia (SIP). Lesions were made in either the “dominant” or “non-dominant” hemisphere as defined by an amphetamine rotation test. It was found that unilateral lesions of either the “dominant” or “non-dominant” SN significantly reduced SIP and also significantly impaired somatosensory responsiveness as indicated by the “tactile extinction test.” Somatosensory neglect was significantly greater following a lesion in the “dominant” hemisphere than “non-dominant” hemisphere.

Asymmetry in the effects of unilateral 6-OHDA lesions on eating and drinking evoked by hypothalamic stimulation

The present experiment investigated the effects of unilateral 6-hydroxydopamine lesions of the caudate nucleus and nucleus accumbens on eating and drinking evoked by electrical stimulation of the lateral hypothalamus (ESLH). Lesions were made on either the ‘dominant’ or ‘non-dominant’ hemisphere as defined by an amphetamine-rotation test. We report here that lesions of the ‘dominant hemisphere’ were significantly more effective in disrupting ESLH-evoked behavior as well as producing longer-lasting deficits in somatosensory responsiveness as measured by the ‘tactile extinction test’.