Baclofen reverses the reduction in prepulse inhibition of the acoustic startle response induced by dizocilpine, but not by apomorphine

Bortolato, Marco; Frau, Roberto; Aru, Gian Nicola; Orrù, Marco; Gessa, Gian Luigi

doi:10.1007/s00213-003-1589-5

Cited by 40 publications

(45 citation statements)

References 51 publications

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“…Consistent with our findings, it was reported that baclofen reversed the reduction in PPI induced by MK-801, but not by apomorphine (a direct dopamine receptor agonist), in rats (Bortolato et al, 2004), and that baclofen and clozapine, but not haloperidol, improved spontaneous PPI deficit in mice (Bortolato et al, 2007). In addition, a recent study (Wolf et al, 2007) demonstrated that acute and subchronic treatment with clozapine failed to ameliorate PPI deficits in mice.…”

Section: Discussionsupporting

confidence: 91%

“…In contrast, a marked reduction of GABA B receptors was reported in the hippocampus and prefrontal cortex (Mizukami et al, 2000;Ishikawa et al, 2005). Although the role of GABA B receptors in schizophrenia and related disorders is still poorly understood, recent pharmacologic studies have demonstrated that baclofen, a GABA B receptor agonist, prevents PPI deficits in rodents (Bortolato et al, 2004(Bortolato et al, , 2007.…”

Section: Introductionmentioning

confidence: 99%

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Involvement of Pallidotegmental Neurons in Methamphetamine- and MK-801-Induced Impairment of Prepulse Inhibition of the Acoustic Startle Reflex in Mice: Reversal by GABAB Receptor Agonist Baclofen

Arai

Takuma

Mizoguchi

et al. 2008

Neuropsychopharmacol

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We have previously demonstrated that pallidotegmental GABAergic neurons play a crucial role in prepulse inhibition (PPI) of the startle reflex in mice through the activation of GABA B receptors in pedunculopontine tegmental neurons. In this study, we investigated whether PPI disruption induced by methamphetamine (METH) or MK-801 is associated with the dysfunction of pallidotegmental neurons. Furthermore, we examined the effects of baclofen, a GABA B receptor agonist, on METH-and MK-801-induced PPI impairment. Acute treatment with METH (3 mg/kg, subcutaneouly (s.c.)) and MK-801 (40.3 mg/kg, s.c.) significantly disrupted PPI, accompanied by the suppression of c-Fos expression in lateral globus pallidus induced by PPI. Furthermore, acute treatment with METH and MK-801 stimulated c-Fos expression in the caudal pontine reticular nucleus (PnC) in mice subjected to the PPT test, although PPI alone had no effect on c-Fos expression. Repeated treatment with 1 mg/kg METH for 7 days, which did not affect PPI acutely, showed similar effects on PPI and c-Fos expression to acute treatment with METH (3 mg/kg). Baclofen dose-dependently ameliorated PPI impairment induced by acute treatment with METH (3 mg/kg) and MK-801 (1 mg/kg), and decreased METH-and MK-801-stimulated c-Fos expression in PnC to the basal level. These results suggest that dysfunction of pallidotegmental neurons is involved in PPI disruption caused by METH and MK-801 in mice. GABA B receptor may constitute a putative target in treating neuropsychiatric disorders with sensorimotor gating deficits, such as schizophrenia and METH psychosis.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Involvement of Pallidotegmental Neurons in Methamphetamine- and MK-801-Induced Impairment of Prepulse Inhibition of the Acoustic Startle Reflex in Mice: Reversal by GABAB Receptor Agonist Baclofen

Arai

Takuma

Mizoguchi

et al. 2008

Neuropsychopharmacol

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“…Startle amplitudes were compared by a three-way ANOVA, with pretreatment and treatment as independent variables and blocks as repeated factors. In keeping with previous findings by our group (Bortolato et al, 2004) Table 2). %PPI analysis, conducted by a second three-way, repeated-measure ANOVA, showed that apomorphine produced a dramatic reduction in PPI, as expected [F(1,80 Topiramate and prepulse inhibition R Frau et al Figure 2, post hoc comparisons revealed that animals treated with TPM + saline exhibited an increased %PPI in comparison with the rats subjected to a double saline injection (po0.01 for each TPM dose, Tukey).…”

Section: Effects Of Tpm Pretreatment Vs Apomorphinesupporting

confidence: 93%

“…As mentioned in the introduction, TPM produces a variety of inhibitory pharmacological and physiological effects relevant to acoustic startle response (ASR), including AMPA receptor antagonism (Gibbs et al, 2000), blockade of voltage-gated Na + channels (Taverna et al, 1999), and particularly GABA activation (White et al, 1997). Assuming that the observed reduction in startle reflex may reflect the GABAergic mechanism of TPM, our data appear to align to previous results from our group, indicating that GABAergic activators determine a dosedependent decrease in startle amplitude (Bortolato et al, 2004). Previous evidence suggests that animals treated with a subchronic administration of TPM exhibit dramatic startle response reductions only after exposure to stressors (Khan and Liberzon, 2004).…”

Section: Effects Of Tpm On Startle Reflexsupporting

confidence: 88%

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Effects of Topiramate on the Prepulse Inhibition of the Acoustic Startle in Rats

Frau

Orrù

Fà

et al. 2006

Neuropsychopharmacol

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The anticonvulsant topiramate (TPM) has been recently proposed as a novel adjuvant therapy for bipolar disorder and schizophrenia, yet its efficacy remains controversial. As both disorders are characterized by gating deficits, we tested the effects of TPM on the behavioral paradigm of prepulse inhibition (PPI) of the acoustic startle response, a validated animal model of sensorimotor gating. TPM (10, 18, 32, 58, 100 mg/kg, intraperitoneal, i.p.) enhanced PPI in rats in a dose-dependent fashion, prevented the PPI reduction mediated by the dopaminergic agonist apomorphine (0.25 mg/kg, subcutaneous, s.c.) and potentiated the effects of the antipsychotic drugs haloperidol (0.05, 0.1 mg/kg, i.p.) and clozapine (2.5, 5 mg/kg, i.p.). Conversely, TPM elicited no significant effect on the PPI disruption mediated by the NMDA receptor antagonist dizocilpine (0.05, 0.1 mg/kg, s.c.) and surprisingly antagonized the attenuation of dizocilpine-induced PPI disruption mediated by clozapine (5 mg/kg, i.p.). Our results suggest that TPM may exert diverse actions on the neural substrates of sensorimotor gating. While the pharmacological mechanisms of such effects are still elusive, our findings might contribute to shed light on some controversies on the therapeutic action of TPM, and point to this drug as a putative novel adjuvant therapy for some clusters of gating disturbances.

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Modulation of stimulated dopamine release in rat nucleus accumbens shell by GABA in vitro: Effect of sub‐chronic phencyclidine pretreatment

Ferdinand

Peters

Yavas

et al. 2021

J of Neuroscience Research

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Dopamine signaling in nucleus accumbens (NAc) is modulated by γ‐aminobutyric acid (GABA), acting through GABA‐A and GABA‐B receptors: dysregulation of GABAergic control of dopamine function may be important in behavioral deficits in schizophrenia. We investigated the effect of GABA‐A (muscimol) and GABA‐B (baclofen) receptor agonists on electrically stimulated dopamine release. Furthermore, we explored whether drug‐induced changes were disrupted by pretreatment with phencyclidine, which provides a well‐validated model of schizophrenia. Using brain slices from female rats, fast‐scan cyclic voltammetry was used to measure electrically stimulated dopamine release in NAc shell. Both muscimol and baclofen caused concentration‐dependent attenuation of evoked dopamine release: neither effect was changed by dihydro‐β‐erythroidine, a nicotinic acetylcholine receptor antagonist, or the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA)‐type glutamate receptor antagonist, 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX), precluding indirect mechanisms using these transmitter systems in the GABAergic actions. In slices taken from rats pretreated with phencyclidine, the attenuation of evoked dopamine release by baclofen was abolished, but the attenuation by muscimol was unaffected. Since phencyclidine pretreatment was followed by drug‐free washout period of at least a week, the drug was not present during recording. Therefore, disruption of GABA‐B modulation of dopamine is due to long‐term functional changes resulting from the treatment, rather than transient changes due to the drug's presence at test. This enduring dysregulation of GABA‐B modulation of accumbal dopamine release provides a plausible mechanism through which GABA dysfunction influences accumbal dopamine leading to behavioral changes seen in schizophrenia and may provide a route for novel therapeutic strategies to treat the condition.

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Baclofen reverses the reduction in prepulse inhibition of the acoustic startle response induced by dizocilpine, but not by apomorphine

Cited by 40 publications

References 51 publications

Involvement of Pallidotegmental Neurons in Methamphetamine- and MK-801-Induced Impairment of Prepulse Inhibition of the Acoustic Startle Reflex in Mice: Reversal by GABAB Receptor Agonist Baclofen

Involvement of Pallidotegmental Neurons in Methamphetamine- and MK-801-Induced Impairment of Prepulse Inhibition of the Acoustic Startle Reflex in Mice: Reversal by GABAB Receptor Agonist Baclofen

Effects of Topiramate on the Prepulse Inhibition of the Acoustic Startle in Rats

Modulation of stimulated dopamine release in rat nucleus accumbens shell by GABA in vitro: Effect of sub‐chronic phencyclidine pretreatment

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