Action of baclofen on mammalian synaptic transmission

Fox, Stephen S.; Krnjević, K.; Morris, Mary E.; Puil, E.; Werman, R.

doi:10.1016/0306-4522(78)90016-7

Cited by 197 publications

(75 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The mechanisms involved in this analgesic effect of baclofen are not yet defined. Saito et al 19 suggested that it may occur by an antagonism to substance P. Other authors suggested that it could be explained by pre-synaptic inhibition of primary afferents or by inhibition of neurotransmitter release from primary afferents 20 , or by involvement of noradrenergic 21 or by cholinergic mechanisms 22. |…”

Section: Discussionmentioning

confidence: 99%

The effect of baclofen on spontaneous and evoked behavioural expression of experimental neuropathic chronic pain

Santos

Castro-Costa

Giffoni

et al. 1999

Arq. Neuro-Psiquiatr.

View full text Add to dashboard Cite

-Baclofen (β-p-chlorophenyl-GABA) has been used in humans to treat spasticity, as well as trigeminal neuralgia. Since GABA (gamma-aminobutyric acid) has been implicated in inhibitory and analgesic effects in the nervous system, it was of interest to study the effect of baclofen in experimental neuropathic pain. With this purpose, experiments were carried out in 17 neuropathic rats with constrictive sciatic injury, as described by Bennet and Xie (1988), taking as pain parameters scratching behaviour and the latency to the thermal nociceptive stimulus. The results showed that baclofen induces, in a dose-dependent manner, significant decrease (p < 0.05) of scratching behaviour and significant increase (p < 0.05) of the latency to the nociceptive thermal stimulus. The absence of antagonism of naloxone suggested a non-participation of an opioid-mediated mechanism in this analgesic effect of baclofen on experimental neuropathic pain.KEY WORDS: baclofen, experimental neuropathic pain, Bennet's model, scratching behaviour, thermal stimulus, analgesia.Efeito do baclofeno sobre a expressão comportamental espontânea e evocada da dor crônica neuropática experimental RESUMO -O baclofeno (β-p-clorofenil-GABA) é usado em seres humanos para tratar espasticidade, assim como neuralgia do trigêmeo. Como o GABA (ácido amino-gama-butírico) tem sido implicado em efeitos inibitórios e analgésicos no sistema nervoso, tornou-se de interesse estudar o efeito do baclofeno em dor neuropática experimental. Com esse objetivo, foram realizados experimentos em 17 ratos neuropáticos com lesão constritiva do nervo ciático, como descrito por Bennet e Xie (1988), tomando como parâmetros de dor o comportamento de coçar-se (scratching) e a latência ao estímulo térmico nociceptivo. Os resultados mostraram que o baclofeno induziu, de forma dose-dependente, diminuição significativa (p < 0,05) do comportamento de coçar-se e aumento significativo (p < 0,05) da latência ao estímulo térmico nociceptivo. A ausência de antagonismo pela naloxona sugere a não participação de mecanismo opióide-mediado nesse efeito analgésico do baclofeno em dor neuropática experimental.PALAVRAS-CHAVE: baclofeno, dor neuropática experimental, modelo de Bennet, comportamento de coçar-se (scratching), estímulos térmicos, analgesia.The study of neuropathic pain remains a serious challenge, since its underlying mechanisms have not yet been elucidated and consequently there is currently a lack of effective treatment. Among the different attempts to alleviate this kind of chronic pain in humans, baclofen (β-p-chlorophenyl-

show abstract

Section: Discussionmentioning

confidence: 99%

The effect of baclofen on spontaneous and evoked behavioural expression of experimental neuropathic chronic pain

Santos

Castro-Costa

Giffoni

et al. 1999

Arq. Neuro-Psiquiatr.

View full text Add to dashboard Cite

show abstract

“…The current therapeutic use of GABA B agonists is mostly restricted to baclofen in the treatment of spasticity. The beneficial antispastic effect of baclofen is believed to derive from the suppression of excitatory neurotransmitter release to motoneurons in the spinal cord (Fox et al 1978 ;Davies, 1981 ;Bonanno et al 1998). Future behavioural studies of baclofen in animal models should help ascertain the potential therapeutic efficacy of this drug for Parkinson's disease and understand better the functions of GABA B in modulating glutamatergic neurotransmission in the basal ganglia circuitry.…”

Section: Metabotropic Glutamate Receptors and Gaba-b Receptors : Potementioning

confidence: 99%

GABA_B and group I metabotropic glutamate receptors in the striatopallidal complex in primates

et al. 2000

View full text Add to dashboard Cite

Glutamate and GABA neurotransmission is mediated through various types of ionotropic and metabotropic receptors. In this review, we summarise some of our recent findings on the subcellular and subsynaptic localisation of GABA B and group I metabotropic glutamate receptors in the striatopallidal complex of monkeys. Polyclonal antibodies that specifically recognise GABA B R1, mGluR1a and mGluR5 receptor subtypes were used for immunoperoxidase and pre-embedding immunogold techniques at the light and electron microscope levels. Both subtypes of group I mGluRs were expressed postsynaptically in striatal projection neurons and interneurons where they aggregate perisynaptically at asymmetric glutamatergic synapses and symmetric dopaminergic synaptic junctions. Moreover, they are also strongly expressed in the main body of symmetric synapses established by putative intrastriatal GABAergic terminals. In the globus pallidus, both receptor subtypes are found postsynaptically in the core of striatopallidal GABAergic synapses and perisynaptically at subthalamopallidal glutamatergic synapses. Finally, extrasynaptic labelling was commonly seen in the globus pallidus and the striatum.Moderate to intense GABA B R1 immunoreactivity was observed in the striatopallidal complex. At the electron microscope level, GABA B R1 immunostaining was commonly found in neuronal cell bodies and dendrites. Many striatal dendritic spines also displayed GABA B R1 immunoreactivity. Moreover, GABA B R1-immunoreactive axons and axon terminals were frequently encountered. In the striatum, GABA B R1-immunoreactive boutons resembled terminals of cortical origin, while in the globus pallidus, subthalamic-like terminals were labelled. Pre-embedding immunogold data showed that postsynaptic GABA B R1 receptors are concentrated at extrasynaptic sites on dendrites, spines and somata in the striatopallidal complex, perisynaptically at asymmetric synapses and in the main body of symmetric striatopallidal synapses in the GPe and GPi. Consistent with the immunoperoxidase data, immunoparticles were found in the presynaptic grid of asymmetric synapses established by cortical-and subthalamic-like glutamatergic terminals.These findings indicate that both GABA and glutamate metabotropic receptors are located to subserve various modulatory functions of the synaptic transmission in the primate striatopallidal complex. Furthermore, their pattern of localisation raises issues about their roles and mechanisms of activation in normal and pathological conditions. Because of their ' modulatory ' functions, these receptors are ideal targets for chronic drug therapies in neurodegenerative diseases such as Parkinson's disease.

show abstract

“…Of particular interest is the observation that baclofen will depress the response of dorsal horn neurones to exogenous excitants (Davies, 1981), implying the existence of a postsynaptic mechanism of action. Intracellular recording from motoneurones has failed to show any effect of systemic baclofen on membrane conductance although synaptic activity is markedly depressed (Pierau & Zimmerman, 1973;Fox et al, 1978). Iontophoretic administration of baclofen to these same neurones does, however, reduce both excitability and membrane input resistance (Fox et al, 1978).…”

mentioning

confidence: 99%

“…Intracellular recording from motoneurones has failed to show any effect of systemic baclofen on membrane conductance although synaptic activity is markedly depressed (Pierau & Zimmerman, 1973;Fox et al, 1978). Iontophoretic administration of baclofen to these same neurones does, however, reduce both excitability and membrane input resistance (Fox et al, 1978).…”

mentioning

confidence: 99%

Actions of the GABA_B agonist, (−)‐baclofen, on neurones in deep dorsal horn of the rat spinal cord in vitro

Allerton

Boden

Hill

1989

British J Pharmacology

View full text Add to dashboard Cite

1 The electrophysiological actions of the GABAB agonist, (-)-baclofen, on deep dorsal horn neurones were studied using an in vitro preparation of the spinal cord of 9-16 day old rat.2 On all neurones tested, (-)-baclofen (100nM-30.uM) had a hyperpolarizing action which was associated with a reduction in apparent membrane input resistance. The increase in membrane conductance was dose-dependent and had a Hill coefficient of 1.0.3 The (-)-baclofen-activated hyperpolarization persisted in the presence of bicuculline (50 gM) and Mg2+ (20mM). 4 The reversal potential of the hyperpolarizing event was estimated at 102 mV and was made less negative by increasing the external concentration of potassium ions. 5 Over the same concentration range, (--baclofen also depressed the polysynaptic composite excitatory postsynaptic potentials (e.p.s.ps) evoked in these neurones by electrical stimulation of the dorsal root entry zone. 6 The potassium channel blockers caesium, applied intracellularly, and barium, applied extracellularly, depressed the postsynaptic response to baclofen but not its effect on e.p.s.ps. 7 We propose that (--baclofen has more than one mechanism of action in spinal dorsal horn: a postsynaptic action mediated via an increase in potassium conductance and a presynaptic action that is not associated with potassium channels and may be mediated via calcium channels. Since previous studies have demonstrated little effect of (-)-baclofen on transmitter release in spinal cord, it is possible that the postsynaptic hyperpolarizing action of (-)-baclofen may account for its clinical potency as an anti-spastic agent.

show abstract

Action of baclofen on mammalian synaptic transmission

Cited by 197 publications

References 47 publications

The effect of baclofen on spontaneous and evoked behavioural expression of experimental neuropathic chronic pain

The effect of baclofen on spontaneous and evoked behavioural expression of experimental neuropathic chronic pain

GABA_B and group I metabotropic glutamate receptors in the striatopallidal complex in primates

Actions of the GABA_B agonist, (−)‐baclofen, on neurones in deep dorsal horn of the rat spinal cord in vitro

Contact Info

Product

Resources

About

Action of baclofen on mammalian synaptic transmission

Cited by 197 publications

References 47 publications

The effect of baclofen on spontaneous and evoked behavioural expression of experimental neuropathic chronic pain

The effect of baclofen on spontaneous and evoked behavioural expression of experimental neuropathic chronic pain

GABAB and group I metabotropic glutamate receptors in the striatopallidal complex in primates

Actions of the GABAB agonist, (−)‐baclofen, on neurones in deep dorsal horn of the rat spinal cord in vitro

Contact Info

Product

Resources

About

GABA_B and group I metabotropic glutamate receptors in the striatopallidal complex in primates

Actions of the GABA_B agonist, (−)‐baclofen, on neurones in deep dorsal horn of the rat spinal cord in vitro