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Irwin Lucki - One of the best experts on this subject based on the ideXlab platform.

  • Noradrenergic lesions differentially alter the antidepressant like effects of reboxetine in a modified forced swim test
    European Journal of Pharmacology, 2002
    Co-Authors: John F. Cryan, Michelle E. Page, Irwin Lucki
    Abstract:

    Abstract The novel antidepressant reboxetine is a selective norepinephrine reuptake inhibitor. In this study, the antidepressant-like effects of reboxetine were characterized in a modified rat forced swim test. Further, in order to investigate the role of the locus coeruleus and lateral tegmental Noradrenergic systems in the mediation of reboxetine's effects, the impact of different chemical lesions of these two pathways was examined on the behavioral responses induced by reboxetine in the forced swim test. Reboxetine (5–20 mg/kg, s.c.) dose-dependently decreased immobility and swimming behavior in the forced swim test while it simultaneously increased climbing behavior. These effects were similar to those previously demonstrated with tricyclic antidepressants and are indicative of reboxetine's effects on the Noradrenergic system. Discrete local injections of the neurotoxin 6-hydroxydopamine were employed to lesion the ventral Noradrenergic Bundle arising from cells located in the lateral tegmentum. This resulting lesion completely prevented reboxetine (10 mg/kg, s.c.)-induced decreases in immobility and increases in climbing behavior, demonstrating that an intact ventral Noradrenergic Bundle is required for the manifestation of reboxetine-induced antidepressant-like behavior in the test. In contrast, lesions of the Dorsal Noradrenergic Bundle which consists of neurons arising from the nucleus locus coereleus, were achieved by systemic pretreatment with the selective Noradrenergic neurotoxin N -(2-chloroethyl)- N -2-bromobenzylamine (DSP-4; 50 mg/kg, i.p.). The ability of reboxetine (10 mg/kg, s.c.) to increase climbing and decrease immobility was augmented by DSP-4 pretreatment. Furthermore, neither lesions of the Dorsal Noradrenergic Bundle nor the ventral Noradrenergic Bundle altered baseline immobility scores in the forced swim test. Taken together, these data suggest that forebrain regions innervated by these two distinct Noradrenergic pathways exert opposing influences on the behavioral response to reboxetine in the rat forced swim test.

  • Noradrenergic lesions differentially alter the antidepressant-like effects of reboxetine in a modified forced swim test
    European Journal of Pharmacology, 2002
    Co-Authors: John F. Cryan, Michelle E. Page, Irwin Lucki
    Abstract:

    The novel antidepressant reboxetine is a selective norepinephrine reuptake inhibitor. In this study, the antidepressant-like effects of reboxetine were characterized in a modified rat forced swim test. Further, in order to investigate the role of the locus coeruleus and lateral tegmental Noradrenergic systems in the mediation of reboxetine's effects, the impact of different chemical lesions of these two pathways was examined on the behavioral responses induced by reboxetine in the forced swim test. Reboxetine (5 - 20 mg/kg, s.c.) dose-dependently decreased immobility and swimming behavior in the forced swim test while it simultaneously increased climbing behavior. These effects were similar to those previously demonstrated with tricyclic antidepressants and are indicative of reboxetine's effects on the Noradrenergic system. Discrete local injections of the neurotoxin 6-hydroxydopamine were employed to lesion the ventral Noradrenergic Bundle arising from cells located in the lateral tegmentum. This resulting lesion completely prevented reboxetine (10 mg/kg, s.c.)-induced decreases in immobility and increases in climbing behavior, demonstrating that an intact ventral Noradrenergic Bundle is required for the manifestation of reboxetine-induced antidepressant-like behavior in the test. In contrast, lesions of the Dorsal Noradrenergic Bundle which consists of neurons arising from the nucleus locus coereleus, were achieved by systemic pretreatment with the selective Noradrenergic neurotoxin N-(2-chloroethyl)-N-2-bromobenzylamine (DSP-4; 50 mg/kg, i.p.). The ability of reboxetine (10 mg/kg, s.c.) to increase climbing and decrease immobility was augmented by DSP-4 pretreatment. Furthermore, neither lesions of the Dorsal Noradrenergic Bundle nor the ventral Noradrenergic Bundle altered baseline immobility scores in the forced swim test. Taken together, these data suggest that forebrain regions innervated by these two distinct Noradrenergic pathways exert opposing influences on the behavioral response to reboxetine in the rat forced swim test. © 2002 Elsevier Science B.V. All rights reserved.

John F. Cryan - One of the best experts on this subject based on the ideXlab platform.

  • Noradrenergic lesions differentially alter the antidepressant like effects of reboxetine in a modified forced swim test
    European Journal of Pharmacology, 2002
    Co-Authors: John F. Cryan, Michelle E. Page, Irwin Lucki
    Abstract:

    Abstract The novel antidepressant reboxetine is a selective norepinephrine reuptake inhibitor. In this study, the antidepressant-like effects of reboxetine were characterized in a modified rat forced swim test. Further, in order to investigate the role of the locus coeruleus and lateral tegmental Noradrenergic systems in the mediation of reboxetine's effects, the impact of different chemical lesions of these two pathways was examined on the behavioral responses induced by reboxetine in the forced swim test. Reboxetine (5–20 mg/kg, s.c.) dose-dependently decreased immobility and swimming behavior in the forced swim test while it simultaneously increased climbing behavior. These effects were similar to those previously demonstrated with tricyclic antidepressants and are indicative of reboxetine's effects on the Noradrenergic system. Discrete local injections of the neurotoxin 6-hydroxydopamine were employed to lesion the ventral Noradrenergic Bundle arising from cells located in the lateral tegmentum. This resulting lesion completely prevented reboxetine (10 mg/kg, s.c.)-induced decreases in immobility and increases in climbing behavior, demonstrating that an intact ventral Noradrenergic Bundle is required for the manifestation of reboxetine-induced antidepressant-like behavior in the test. In contrast, lesions of the Dorsal Noradrenergic Bundle which consists of neurons arising from the nucleus locus coereleus, were achieved by systemic pretreatment with the selective Noradrenergic neurotoxin N -(2-chloroethyl)- N -2-bromobenzylamine (DSP-4; 50 mg/kg, i.p.). The ability of reboxetine (10 mg/kg, s.c.) to increase climbing and decrease immobility was augmented by DSP-4 pretreatment. Furthermore, neither lesions of the Dorsal Noradrenergic Bundle nor the ventral Noradrenergic Bundle altered baseline immobility scores in the forced swim test. Taken together, these data suggest that forebrain regions innervated by these two distinct Noradrenergic pathways exert opposing influences on the behavioral response to reboxetine in the rat forced swim test.

  • Noradrenergic lesions differentially alter the antidepressant-like effects of reboxetine in a modified forced swim test
    European Journal of Pharmacology, 2002
    Co-Authors: John F. Cryan, Michelle E. Page, Irwin Lucki
    Abstract:

    The novel antidepressant reboxetine is a selective norepinephrine reuptake inhibitor. In this study, the antidepressant-like effects of reboxetine were characterized in a modified rat forced swim test. Further, in order to investigate the role of the locus coeruleus and lateral tegmental Noradrenergic systems in the mediation of reboxetine's effects, the impact of different chemical lesions of these two pathways was examined on the behavioral responses induced by reboxetine in the forced swim test. Reboxetine (5 - 20 mg/kg, s.c.) dose-dependently decreased immobility and swimming behavior in the forced swim test while it simultaneously increased climbing behavior. These effects were similar to those previously demonstrated with tricyclic antidepressants and are indicative of reboxetine's effects on the Noradrenergic system. Discrete local injections of the neurotoxin 6-hydroxydopamine were employed to lesion the ventral Noradrenergic Bundle arising from cells located in the lateral tegmentum. This resulting lesion completely prevented reboxetine (10 mg/kg, s.c.)-induced decreases in immobility and increases in climbing behavior, demonstrating that an intact ventral Noradrenergic Bundle is required for the manifestation of reboxetine-induced antidepressant-like behavior in the test. In contrast, lesions of the Dorsal Noradrenergic Bundle which consists of neurons arising from the nucleus locus coereleus, were achieved by systemic pretreatment with the selective Noradrenergic neurotoxin N-(2-chloroethyl)-N-2-bromobenzylamine (DSP-4; 50 mg/kg, i.p.). The ability of reboxetine (10 mg/kg, s.c.) to increase climbing and decrease immobility was augmented by DSP-4 pretreatment. Furthermore, neither lesions of the Dorsal Noradrenergic Bundle nor the ventral Noradrenergic Bundle altered baseline immobility scores in the forced swim test. Taken together, these data suggest that forebrain regions innervated by these two distinct Noradrenergic pathways exert opposing influences on the behavioral response to reboxetine in the rat forced swim test. © 2002 Elsevier Science B.V. All rights reserved.

Michelle E. Page - One of the best experts on this subject based on the ideXlab platform.

  • Noradrenergic lesions differentially alter the antidepressant like effects of reboxetine in a modified forced swim test
    European Journal of Pharmacology, 2002
    Co-Authors: John F. Cryan, Michelle E. Page, Irwin Lucki
    Abstract:

    Abstract The novel antidepressant reboxetine is a selective norepinephrine reuptake inhibitor. In this study, the antidepressant-like effects of reboxetine were characterized in a modified rat forced swim test. Further, in order to investigate the role of the locus coeruleus and lateral tegmental Noradrenergic systems in the mediation of reboxetine's effects, the impact of different chemical lesions of these two pathways was examined on the behavioral responses induced by reboxetine in the forced swim test. Reboxetine (5–20 mg/kg, s.c.) dose-dependently decreased immobility and swimming behavior in the forced swim test while it simultaneously increased climbing behavior. These effects were similar to those previously demonstrated with tricyclic antidepressants and are indicative of reboxetine's effects on the Noradrenergic system. Discrete local injections of the neurotoxin 6-hydroxydopamine were employed to lesion the ventral Noradrenergic Bundle arising from cells located in the lateral tegmentum. This resulting lesion completely prevented reboxetine (10 mg/kg, s.c.)-induced decreases in immobility and increases in climbing behavior, demonstrating that an intact ventral Noradrenergic Bundle is required for the manifestation of reboxetine-induced antidepressant-like behavior in the test. In contrast, lesions of the Dorsal Noradrenergic Bundle which consists of neurons arising from the nucleus locus coereleus, were achieved by systemic pretreatment with the selective Noradrenergic neurotoxin N -(2-chloroethyl)- N -2-bromobenzylamine (DSP-4; 50 mg/kg, i.p.). The ability of reboxetine (10 mg/kg, s.c.) to increase climbing and decrease immobility was augmented by DSP-4 pretreatment. Furthermore, neither lesions of the Dorsal Noradrenergic Bundle nor the ventral Noradrenergic Bundle altered baseline immobility scores in the forced swim test. Taken together, these data suggest that forebrain regions innervated by these two distinct Noradrenergic pathways exert opposing influences on the behavioral response to reboxetine in the rat forced swim test.

  • Noradrenergic lesions differentially alter the antidepressant-like effects of reboxetine in a modified forced swim test
    European Journal of Pharmacology, 2002
    Co-Authors: John F. Cryan, Michelle E. Page, Irwin Lucki
    Abstract:

    The novel antidepressant reboxetine is a selective norepinephrine reuptake inhibitor. In this study, the antidepressant-like effects of reboxetine were characterized in a modified rat forced swim test. Further, in order to investigate the role of the locus coeruleus and lateral tegmental Noradrenergic systems in the mediation of reboxetine's effects, the impact of different chemical lesions of these two pathways was examined on the behavioral responses induced by reboxetine in the forced swim test. Reboxetine (5 - 20 mg/kg, s.c.) dose-dependently decreased immobility and swimming behavior in the forced swim test while it simultaneously increased climbing behavior. These effects were similar to those previously demonstrated with tricyclic antidepressants and are indicative of reboxetine's effects on the Noradrenergic system. Discrete local injections of the neurotoxin 6-hydroxydopamine were employed to lesion the ventral Noradrenergic Bundle arising from cells located in the lateral tegmentum. This resulting lesion completely prevented reboxetine (10 mg/kg, s.c.)-induced decreases in immobility and increases in climbing behavior, demonstrating that an intact ventral Noradrenergic Bundle is required for the manifestation of reboxetine-induced antidepressant-like behavior in the test. In contrast, lesions of the Dorsal Noradrenergic Bundle which consists of neurons arising from the nucleus locus coereleus, were achieved by systemic pretreatment with the selective Noradrenergic neurotoxin N-(2-chloroethyl)-N-2-bromobenzylamine (DSP-4; 50 mg/kg, i.p.). The ability of reboxetine (10 mg/kg, s.c.) to increase climbing and decrease immobility was augmented by DSP-4 pretreatment. Furthermore, neither lesions of the Dorsal Noradrenergic Bundle nor the ventral Noradrenergic Bundle altered baseline immobility scores in the forced swim test. Taken together, these data suggest that forebrain regions innervated by these two distinct Noradrenergic pathways exert opposing influences on the behavioral response to reboxetine in the rat forced swim test. © 2002 Elsevier Science B.V. All rights reserved.

Leon J Thal - One of the best experts on this subject based on the ideXlab platform.

  • comparison of the effects of single and combined neurotoxic lesions of the nucleus basalis magnocellularis and Dorsal Noradrenergic Bundle on learning and memory in the rat
    Behavioural Brain Research, 1993
    Co-Authors: Philip J Langlais, Donald J Connor, Leon J Thal
    Abstract:

    Abstract Groups of rats received bilateral destruction of either the nucleus basalis magnocellularis (NBM) by infusion of ibotenic acid, the Dorsal Noradrenergic Bundle (DNB) by infusion of 6-hydroxydopamine, or both NBM + DNB (COMB). These lesion groups along with sham operated controls were trained on a food reinforced spatial delayed conditional discrimination task in a T-maze. All four groups were able to attain a criterion of 85% correct responses despite significant group differences in the number of trials to criterion and number of correct responses during training. Performance of the DNB and NBM groups on acquisition trials was significantly lower than controls, significantly higher than the COMB group, but not significantly different from each other. When tested at delays of 30–300 s, all groups demonstrated parallel rates of decline in performance. On reversal learning trials, the NBM and COMB groups were significantly impaired, whereas the performance of the DNB group was better than controls. No significant interaction between the DNB and NBM lesions was observed on any of the behavioral measures. Biochemical analyses demonstrated significant reductions of choline acetyltransferase (ChAT) activity in cortex but not hippocampus of the NBM and COMB groups, and a significant reduction of norepinephrine (NE) in cortex and hippocampus of the DNB and COMB but not the NBM group. The concentration of other monoamine and amino acid neurotransmitters in the lesion groups were unchanged from controls. These results suggest that DNB and NBM lesions produce separate and independent cognitive impairments that do not severely disrupt retention of trial independent (reference memory) and trial dependent (working memory) information on this T-maze task.

  • behavioral effects of concurrent lesions of the nucleus basalis magnocellularis and the Dorsal Noradrenergic Bundle
    Experimental Neurology, 1992
    Co-Authors: Donald J Connor, Philip J Langlais, Suzan Dietz, Leon J Thal
    Abstract:

    Abstract The effects of separate and concurrent lesions to the cholinergic and Noradrenergic (NE) systems were assessed in two water mazes. Lesion of the nucleus basalis magnocellularis (NBM) decreased performance in a spatial memory task (Morris water maze) while lesions of the Dorsal NE Bundle (DNB) enhanced the acquisition of this task independent of the NBM effects. Both lesions impaired performance on a water-escape motivated T-maze; however, the deficits induced by the combined lesion did not differ from the effects of either lesion alone. Neither lesion, nor their combination, had significant effects on open field activity. Biochemical analyses revealed almost total loss of NE in the cortex and hippocampus after DNB lesion, with relatively minor changes in other catecholamines or metabolites. Choline acetyltransferase activity was not significantly altered by the DNB lesion but was decreased in the cortex by the NBM lesion. These results suggest a task-specific effect of DNB lesion that is detectable under conditions of mild stress when floor effects are minimized.

Trevor W Robbins - One of the best experts on this subject based on the ideXlab platform.

  • lesions of the Dorsal Noradrenergic Bundle impair attentional set shifting in the rat
    European Journal of Neuroscience, 2007
    Co-Authors: David S Tait, Verity J Brown, Anja Farovik, David E H Theobald, Jeffrey W Dalley, Trevor W Robbins
    Abstract:

    : Rats with medial prefrontal cortex (mPFC) lesions are impaired in attentional set-shifting, when it is required to shift to a previously irrelevant perceptual dimension. The main source of Noradrenergic input to the mPFC is from the locus coeruleus via the Dorsal Noradrenergic ascending Bundle (DNAB). This study examined the effects of selective cortical noradrenaline depletion following 6-hydroxydopamine-induced lesions of the DNAB on attentional set-shifting and other aspects of discrimination learning and performance. Rats learned to dig in baited bowls, and then acquired discriminations based on one of two aspects of a bowl--odour or digging medium. The task tested acquisition of novel discriminations (both intra- and extra-dimensional) and reversal learning when contingencies were reversed with the same stimuli. At the conclusion of testing, the DNAB-lesioned rats were shown to have a selective depletion of noradrenaline of approximately 70% within the mPFC (cingulate and prelimbic cortex subregions), with no other significant changes in dopamine or 5-hydroxytryptamine. Rats required more trials to learn new discriminations when attentional shifting was required [extra-dimensional (ED)-shift]. Rats with Dorsal Noradrenergic ascending Bundle (DNAB) lesions were impaired in novel acquisitions when an ED-shift was required, but were unimpaired in reversal learning and other aspects of discrimination learning, relative to controls. These data are consistent with other evidence implicating noradrenaline (NA) in attentional set-shifting, and contrast with effects of manipulations of 5-hydroxytryptamine (5-HT) and acetylcholine within the medial prefrontal cortex (mPFC). The findings are also relevant to recent theorizing about the functions of the coeruleo-cortical Noradrenergic system.