Drug-induced modulation of locomotor hyperactivity induced by picrotoxin in nucleus accumbens

Morgenstern, Rudolf; Mende, Thomas J.; Gold, R; Lemme, P.; Oelssner, W

doi:10.1016/s0091-3057(84)80030-1

Cited by 32 publications

(16 citation statements)

References 39 publications

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“…Supporting our findings, microinjection of various doses of NT into the mPFC has also been shown to have no effect on basal locomotor activity of rats (Radcliffe and Erwin, 1996). Disrupting the activity of neurons in the NAc pharmacologically or by lesioning has been reported to alter locomotor activity (Donzanti and Uretsky, 1983; Fink and Smith, 1980; Ikemoto, 2002; Kelly et al, 1976; Morgenstern et al, 1984; Pycock and Horton, 1979; Schwarting and Huston, 1996). Moreover, microinjection of NT into the NAc has been shown to inhibit dopamine- and psychostimulant-mediated hyperactivity (Ervin et al, 1981; Kalivas et al, 1984; Robledo et al, 1993; Steinberg et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Activation of neurotensin receptor type 1 attenuates locomotor activity

et al. 2014

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Intracerebroventricular administration of neurotensin (NT) suppresses locomotor activity. However, the brain regions that mediate the locomotor depressant effect of NT and receptor subtype-specific mechanisms involved are unclear. Using a brain-penetrating, selective NT receptor type 1 (NTS1) agonist PD149163, we investigated the effect of systemic and brain region-specific NTS1 activation on locomotor activity. Systemic administration of PD149163 attenuated the locomotor activity of C57BL/6J mice both in a novel environment and in their homecage. However, mice developed tolerance to the hypolocomotor effect of PD149163 (0.1 mg/kg, i.p.). Since NTS1 is known to modulate dopaminergic signaling, we examined whether PD149163 blocks dopamine receptor-mediated hyperactivity. Pretreatment with PD149163 (0.1 or 0.05 mg/kg, i.p.) inhibited D2R agonist bromocriptine (8 mg/kg, i.p.)-mediated hyperactivity. D1R agonist SKF81297 (8 mg/kg, i.p.)-induced hyperlocomotion was only inhibited by 0.1 mg/kg of PD149163. Since the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) have been implicated in the behavioral effects of NT, we examined whether microinjection of PD149163 into these regions reduces locomotion. Microinjection of PD149163 (2 pmol) into the NAc, but not the mPFC suppressed locomotor activity. In summary, our results indicate that systemic and intra-NAc activation of NTS1 is sufficient to reduce locomotion and NTS1 activation inhibits D2R-mediated hyperactivity. Our study will be helpful to identify pharmacological factors and a possible therapeutic window for NTS1-targeted therapies for movement disorders.

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Section: Discussionmentioning

confidence: 99%

Activation of neurotensin receptor type 1 attenuates locomotor activity

et al. 2014

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“…A second factor that should be further investigated is the coincident emergence of hyperactivity with myoclonic movements and seizure activity in APP 751 SWE mice (Dumont et al, 2004). These results point to a possible contribution of impaired GABAergic transmission in the hyperactive phenotype, since GABA A receptor antagonists increase motor activity in rats, for example picrotoxin injected at subconvulsive doses either in the periphery (Chang et al, 2004) or directly into the hippocampus (Bast et al, 2001), amygdala (Chang et al, 2004), or nucleus accumbens (Morgenstern et al, 1984). …”

Section: Exploratory Activity In Alzheimer Micementioning

confidence: 95%

APP transgenic mice for modelling behavioural and psychological symptoms of dementia (BPSD)

Lalonde

Fukuchi

Strazielle

2012

Neuroscience & Biobehavioral Reviews

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The discovery of gene mutations responsible for autosomal dominant Alzheimer's disease has enabled researchers to reproduce in transgenic mice several hallmarks of this disorder, notably Aβ accumulation, though in most cases without neurofibrillary tangles. Mice expressing mutated and wild-type APP as well as C-terminal fragments of APP exhibit variations in exploratory activity reminiscent of behavioral and psychological symptoms of Alzeimer dementia (BPSD). In particular, open-field, spontaneous alternation, and elevated plus-maze tasks as well as aggression are modified in several APP transgenic mice relative to non-transgenic controls. However, depending on the precise murine models, changes in open-field and elevated plus-maze exploration occur in either direction, either increased or decreased relative to controls. It remains to be determined which neurotransmitter changes are responsible for this variability, in particular with respect to GABA, 5HT, and dopamine.

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“…2B) gion may differ in localization of G E A A receptors on resynaptic terminals from the more lateral striatum. 5 he possibility that dopamine terminals in the nucleus accumbens may contain a ortion of the GABAA receptor PO ulation is supporte B by behavioral observations that tRe motor effect of GABAA agonists and antagonists microinjected into the nucleus accumbens involves dopamine neurotransmission (Hartgraves and Kelly, 1983;Morgenstern et al, 1984;Pycock and Horton, 1976;Sivam et al, 1987). Furthermore, by combined electron microsco y and immunocytochemistry, it was on tyrosine hydroxylase-containing terminals in the nucleus accumbens (Pickel et al, 1988).…”

Section: MMmentioning

confidence: 98%

GABA_A receptors containing α₁ and β₂ subunits are mainly localized on neurons in the ventral pallidum

Churchill

Bourdelais

Austin

et al. 1991

Synapse

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The gamma-aminobutyric acid (GABA) projection from the nucleus accumbens to the ventral pallidum (VP) is important in the regulation of locomotion. Thus, stimulation and inhibition of GABAA receptors in the VP can alter locomotor activity. To determine whether the GABAA receptors are located presynaptically on accumbens efferents to the VP or postsynaptically on neurons intrinsic to the VP two experiments were performed. In the first, quinolinic acid lesions of the nucleus accumbens did not alter [3H]muscimol binding in the VP, while lesions in the VP significantly reduced (60-80%) binding as measured by light microscopic receptor autoradiography. In the second experiment, in situ hybridization with oligonucleotide probes for mRNAs of the alpha 1 and beta 2 subunits of the GABAA receptor was examined in the nucleus accumbens and VP. No mRNA for either subunit was observed in the nucleus accumbens, although many positively labeled neurons were present within the VP. By contrast, a moderate to high density of cells in both the nucleus accumbens and VP contained mRNA for glutamic acid decarboxylase. These data argue that the majority of GABAA receptors in the VP are not located presynaptically on axonal terminals originating from neurons in the nucleus accumbens.

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Drug-induced modulation of locomotor hyperactivity induced by picrotoxin in nucleus accumbens

Cited by 32 publications

References 39 publications

Activation of neurotensin receptor type 1 attenuates locomotor activity

Activation of neurotensin receptor type 1 attenuates locomotor activity

APP transgenic mice for modelling behavioural and psychological symptoms of dementia (BPSD)

GABA_A receptors containing α₁ and β₂ subunits are mainly localized on neurons in the ventral pallidum

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Drug-induced modulation of locomotor hyperactivity induced by picrotoxin in nucleus accumbens

Cited by 32 publications

References 39 publications

Activation of neurotensin receptor type 1 attenuates locomotor activity

Activation of neurotensin receptor type 1 attenuates locomotor activity

APP transgenic mice for modelling behavioural and psychological symptoms of dementia (BPSD)

GABAA receptors containing α1 and β2 subunits are mainly localized on neurons in the ventral pallidum

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GABA_A receptors containing α₁ and β₂ subunits are mainly localized on neurons in the ventral pallidum