Mechanisms of general anesthesia: Brain regional ersponses to baclofen

Lewis, Johnnye; Westerberg, Verner S.; LaBella, Frank S.

doi:10.1016/0031-9384(89)90310-7

Cited by 4 publications

(2 citation statements)

References 28 publications

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“…Therefore, reductions in self-administration could be due to the nonspecific actions of these agonists and not necessarily to decreases in the reinforcing nature of the drug of abuse. Addressing the sedative effects of baclofen are especially pertinent in alcohol self-administration studies given that, at certain doses, both baclofen and ethanol alone can have sedative and motor impairing/locomotor depressing properties (Lewis et al 1989;De Luca and Massotti 1990;Middaugh et al 1992;gmo and Soria 1997;Munzar et al 2000). Thus, co-administration of baclofen and alcohol could potentially result in enhancement of the sedative properties of either compound.…”

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confidence: 97%

GABAB receptor agonists reduce operant ethanol self-administration and enhance ethanol sedation in C57BL/6J mice

2004

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GABA(B) agonists decrease the reinforcing effects of ethanol at doses that inhibit locomotor activity and potentiate the sedative hypnotic effects of ethanol. These nonspecific effects of GABA(B) agonists were reduced in alcohol experienced mice, suggesting cross-tolerance to the inhibitory properties of GABA(B) positive modulation. These data question the safety of prescribing GABA(B) agonists to alcoholics since these drugs may potentiate ethanol's sedative/hypnotic effects during relapse.

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confidence: 97%

GABAB receptor agonists reduce operant ethanol self-administration and enhance ethanol sedation in C57BL/6J mice

2004

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“…The animals retain, however, the reactivity to environmental stimuli. Similarly, Lewis et al (1989) reported that baclofen given intraperitoneally or intraventricularly (10 and 20 gg) failed to elicit strictly defined ,,anesthesia". The animals continued to show motor responses when handled and retained corneal reflexes.…”

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confidence: 96%

Myorelaxant effect of baclofen injected to the nucleus accumbens septi

Roman

Płaźnik

Palejko

et al. 1990

J Neural Transm Gen Sect

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The GABAergic modulation in the nucleus accumbens septi (NAS) of muscle tone was investigated in rats using behavioral tests. The GABAB receptor agonist baclofen dose-dependently decreased muscle tone in the wire-mesh and bar holding tests both after local injection into the NAS (1.0 and 2.5 micrograms), and after intraperitoneal administration in a dose of 20 mg/kg. In the Wirth's test haloperidol (5 mg/kg i.p.), produced catalepsy, whereas baclofen (20 mg/kg, i.p.) significantly deteriorated rats' performance. Intraaccumbens microinjections of muscimol, midazolam, nicardipine, as well as peripheral injections of haloperidol and midazolam failed to modify muscle tone in the wire-mesh test. These findings argue against the involvement of GABAA receptors, benzodiazepine receptors, as well as dopaminergic- and calcium channel-related mechanisms in the effect of baclofen. Hence, the muscle relaxant effect of baclofen seems to be also mediated through GABAB receptor sites within the NAS.

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GABA and Epilepsy: Their Complex Relationship and the Evolution of Our Understanding

Snodgrass

1992

J Child Neurol

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Because of its abundance in the brain, its ability to produce hyperpolarizing inhibition of almost all neurons, its association with benzodiazepines, and the discovery that many convulsants inhibited its synthesis, gamma-aminobutyric acid (GABA) has often appeared to be the key to epilepsy. Many assumed that "primary" or "genetic" epilepsy must be a disorder of GABA synapses and that GABA agonists would be universal anticonvulsants if permeability and drug metabolism were controlled. The GABA synthetic gene was a logical "candidate gene" for epilepsy. However, the GABA-deficiency theory of epilepsy is less convincing today. GABA agonists were found to intensify seizures in some rodent and human cases. Absence and other generalized seizures in humans often worsened when treated with GABA transaminase inhibitors such as gamma-vinyl-GABA. Surprisingly, the GABA transaminase inhibitors appear to be more useful in partial than in generalized epilepsies. Neuronal GABA uptake blockers are proconvulsant. GABA agonists aggravate seizures in several mutants, ranging from the photosensitive baboon to the genetically epilepsy-prone rat. How can this be understood? Muscimol injections into the pedunculopontine nucleus increase seizures due to systematically administered convulsants, while the receptor blocker bicuculline suppresses seizures after injection into several brain regions, including the striatum. The result of inhibiting inhibitory circuits is excitation. Studies with GABA uptake blockers and the GABAB agonist baclofen are presented in which their combined administration provoked seizures in rats. Baclofen was shown also to increase the incidence of seizures evoked by pentylenetetrazole without increasing seizures due to local injections of excitatory amino acids. Baclofen antagonized the myoclonic effect of 5-hydroxytryptophan in rats with serotonin lesions. Baclofen augments some seizures and inhibits others. Selective inhibition of a particular tract, whether GABAergic or not, may have convulsant or anticonvulsant effects, depending on its connections and the state of the organism. GABAA receptor stimulation is usually but not always anticonvulsant. GABAB receptor stimulation may facilitate absence seizures and related primary generalized seizures. GABAB receptors may be abnormal in some forms of nonfocal epilepsy seen in childhood. It is likely that mutations of GABA transporter and GABAA receptor genes will be found in humans but they will probably not be patients with "pure epilepsy."

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Mechanisms of general anesthesia: Brain regional ersponses to baclofen

Cited by 4 publications

References 28 publications

GABAB receptor agonists reduce operant ethanol self-administration and enhance ethanol sedation in C57BL/6J mice

GABAB receptor agonists reduce operant ethanol self-administration and enhance ethanol sedation in C57BL/6J mice

Myorelaxant effect of baclofen injected to the nucleus accumbens septi

GABA and Epilepsy: Their Complex Relationship and the Evolution of Our Understanding

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