Pharmacological modulation of GABAB receptors affects cocaine-induced seizures in mice

Gąsior, Maciej; Kamiński, Rafał M.; Witkin, Jeffrey M.

doi:10.1007/s00213-003-1743-0

Cited by 16 publications

(7 citation statements)

References 35 publications

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“…Cocaine decreases GABA activity through alternations in the function of ion channels, in particular sodium and calcium channels, leading to an increase in excitatory neurotransmission. 7,22,29 Increased serotonin neurotransmission due to decreased serotonin reuptake has also been implicated in cocaine-induced seizures. 17 The 5-HT2 receptors appear to play a significant role in this effect.…”

Section: Discussionmentioning

confidence: 99%

Cocaine use as an independent predictor of seizures after aneurysmal subarachnoid hemorrhage

Chang

Kowalski²,

Carhuapoma

et al. 2016

JNS

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OBJECT Seizures are relatively common after aneurysmal subarachnoid hemorrhage (aSAH). Seizure prophylaxis is controversial and is often based on risk stratification; middle cerebral artery (MCA) aneurysms, associated intracerebral hemorrhage (ICH), poor neurological grade, increased clot thickness, and cerebral infarction are considered highest risk for seizures. The purpose of this study was to evaluate the impact of recent cocaine use on seizure incidence following aSAH. METHODS Prospectively collected data from aSAH patients admitted to 2 institutional neuroscience critical care units between 1991 and 2009 were reviewed. The authors analyzed factors that potentially affected the incidence of seizures, including patient demographic characteristics, poor clinical grade (Hunt and Hess Grade IV or V), medical comorbidities, associated ICH, intraventricular hemorrhage (IVH), hydrocephalus, aneurysm location, surgical clipping and cocaine use. They further studied the impact of these factors on “early” and “late” seizures (defined, respectively, as occurring before and after clipping/coiling). RESULTS Of 1134 aSAH patients studied, 182 (16%) had seizures; 81 patients (7.1%) had early and 127 (11.2%) late seizures, with 26 having both. The seizure rate was significantly higher in cocaine users (37 [26%] of 142 patients) than in non-cocaine users (151 [15.2%] of 992 patients, p = 0.001). Eighteen cocaine-positive patients (12.7%) had early seizures compared with 6.6% of cocaine-negative patients (p = 0.003); 27 cocaine users (19%) had late seizures compared with 10.5% non-cocaine users (p = 0.001). Factors that showed a significant association with increased risk for seizure (early or late) on univariate analysis included younger age (< 40 years) (p = 0.009), poor clinical grade (p = 0.029), associated ICH (p = 0.007), and MCA aneurysm location (p < 0.001); surgical clipping was associated with late seizures (p = 0.004). Following multivariate analysis, age < 40 years (OR 2.04, 95% CI 1.355–3.058, p = 0.001), poor clinical grade (OR 1.62, 95% CI 1.124–2.336, p = 0.01), ICH (OR 1.95, 95% CI 1.164–3.273, p = 0.011), MCA aneurysm location (OR 3.3, 95% CI 2.237–4.854, p < 0.001), and cocaine use (OR 2.06, 95% CI 1.330–3.175, p = 0.001) independently predicted seizures. CONCLUSIONS Cocaine use confers a higher seizure risk following aSAH and should be considered during risk stratification for seizure prophylaxis and close neuromonitoring.

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Section: Discussionmentioning

confidence: 99%

Cocaine use as an independent predictor of seizures after aneurysmal subarachnoid hemorrhage

Chang

Kowalski²,

Carhuapoma

et al. 2016

JNS

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“…Cocaine causes an enhancement of NMDA/AMPA glutamate transmission and can promote induction of LTP in the VTA (Ungless, et al, 2001; Borgland, et al, 2004); increased excitability of DA VTA neurons due to reduced DA autoinhibition and reduced GABA B inhibition may help promote such LTP. At the whole animal level, cocaine-induced seizures are attenuated by GABA B agonists and potentiated by GABA B agonists (Gasior, et al, 2004), suggesting an interaction between monoamine reuptake blockade and GABA B function. Understanding molecular mechanisms underlying the effects of sustained increases in dopamine or GABA concentration in the VTA may contribute to medication discovery for more effective treatment of disorders related to addiction.…”

Section: Discussionmentioning

confidence: 99%

Reversal of inhibition of putative dopaminergic neurons of the ventral tegmental area: Interaction of GABAB and D2 receptors

et al. 2012

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Neurons of the ventral tegmental area (VTA) are critical in the rewarding and reinforcing properties of drugs of abuse. Desensitization of VTA neurons to moderate extracellular concentrations of dopamine (DA) is dependent on protein kinase C (PKC) and intracellular calcium levels. This desensitization is called DA inhibition reversal (DIR), as it requires concurrent activation of D2 and D1-like receptors; activation of D2 receptors alone does not result in desensitization. Activation of other G-protein linked receptors can substitute for D1 activation. Like D2 receptors, GABAB receptors in the VTA are coupled to G-protein-linked potassium channels. In the present study, we examined interactions between a GABAB agonist, baclofen, and dopamine agonists, dopamine and quinpirole, to determine whether there was some interaction in the processes of desensitization of GABAB and D2 responses. Long-duration administration of baclofen alone produced reversal of the baclofen-induced inhibition indicative of desensitization, and this desensitization persisted for at least 60 min after baclofen washout. Desensitization to baclofen was dependent on protein kinase C. Dopamine inhibition was reduced for 30 min after baclofen-induced desensitization and conversely, the magnitude of baclofen inhibition was reduced for 30 min by long-duration application of dopamine, but not quinpirole. These results indicate that D2 and GABAB receptors share some protein kinase C-dependent mechanisms of receptor desensitization.

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“…GABA B agonists, in particular, show promise as potential treatment medications for cocaine abuse (Brebner et al, 2002;. In rodents, pretreatment with GABA B agonists dose-dependently reduced the cocaine-induced DA release in mesolimbic regions (Fadda et al, 2003), reduced cocaine-induced facilitation of brain stimulation reward (Dobrovitsky et al, 2002), and decreased cocaine-induced seizures (Gasior et al, 2004). Baclofen, the prototypical GABA B agonist, has been reported to decrease cocaine self-administration in rats (Roberts et al, 1996;Roberts & Andrews, 1997).…”

Section: Introductionmentioning

confidence: 99%

Attenuation of cocaine-seeking by GABAB receptor agonists baclofen and CGP44532 but not the GABA reuptake inhibitor tiagabine in baboons

Weerts

Froestl

Kaminski

et al. 2007

Drug and Alcohol Dependence

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The current study evaluated the effects of drugs that increase GABA levels by activation of GABA(B) receptors (baclofen and CGP44532) or by inhibition of GABA reuptake (tiagabine) on the reinstatement of extinguished lever responding produced by priming doses of cocaine in baboons (i.e., cocaine-seeking). Cocaine self-injection was established and maintained under a fixed ratio (FR10) schedule of reinforcement during daily 2h sessions. Lever responding was extinguished by substituting vehicle (saline) for cocaine until the number of self-injections decreased to 10 or less per session for two consecutive sessions (defined as extinction). Once extinction occurred, priming doses of cocaine (0.1-3.2mg/kg, i.v.) were administered during extinction conditions. Administration of priming doses of cocaine significantly increased cocaine-seeking in a dose-dependent manner. Cocaine-seeking produced by priming doses of cocaine were attenuated by pretreatment with baclofen (N=5) or CGP44532 (N=5) but not tiagabine (N=3). The doses of baclofen (0.32 mg/kg), and CGP445532 (0.32 mg/kg) that reduced cocaine-seeking produced by cocaine priming doses did not reinstate cocaine-seeking and did not produce overt effects when administered alone. These data indicate that GABA(B) agonists may reduce relapse to cocaine taking.

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Pharmacological modulation of GABAB receptors affects cocaine-induced seizures in mice

Abstract: Modulation of GABA(B) receptors can affect seizures induced by cocaine. This molecular mechanism may be involved in seizures induced by cocaine or, alternatively, may function as an independent inhibitory mechanism against seizures arising from blockade of monoamine uptake.

Cited by 16 publications

References 35 publications

Cocaine use as an independent predictor of seizures after aneurysmal subarachnoid hemorrhage

Cocaine use as an independent predictor of seizures after aneurysmal subarachnoid hemorrhage

Reversal of inhibition of putative dopaminergic neurons of the ventral tegmental area: Interaction of GABAB and D2 receptors

Attenuation of cocaine-seeking by GABAB receptor agonists baclofen and CGP44532 but not the GABA reuptake inhibitor tiagabine in baboons

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