Search PubMed⌕ Search

Biomedical subjects

C Marescaux

Publications and source records attributed to C Marescaux.

At least 91 records · Page 5Linked to original sources
PubMed1998

Mapping of neuronal networks underlying generalized seizures induced by increasing doses of pentylenetetrazol in the immature and adult rat: a c-Fos immunohistochemical study.

Previous studies from our group have shown that pentylenetetrazol (PTZ)-induced status epilepticus (SE) leads to age-dependent acute and long-term metabolic and circulatory changes in immature rats. In order to define the neural substrates involved in PTZ seizures according to age, the purpose of the present study was to map the areas of cellular activation during seizures of increasing severity in 10-day-old (P10), 21-day-old (P21) and adult rats. Seizures were induced by repetitive injections of subconvulsive doses of PTZ. The total dose received by the animals ranged from 4 to 125 mg/kg. These doses induced a variety of seizure profiles including absence-like, clonic seizures and SE. The cellular activation was measured as the density of c-Fos immunoreactive cells in animals at 2 h after the onset of the seizures. In P10 rats receiving a behaviourally non-active dose of PTZ, c-Fos immunoreactivity appeared only in the amygdala. The dose of 40 mg/kg that induced absence-like seizures led to a weak c-Fos expression in the medial thalamus, some cortical areas and globus pallidus. Clonic seizures reinforced labelling in the previous areas and induced a spread of c-Fos immunoreactivity to other cortical areas, thalamus, hypothalamus and some brainstem nuclei. At that age, only SE led to a widespread and stronger expression of c-Fos which was, however, totally lacking in the midbrain, and remained incomplete in the brainstem and forebrain limbic system, including the hippocampus. In P21 and adult rats, the inactive dose of PTZ induced c-Fos immunoreactivity in thalamus and hypothalamus. With absence-like seizures, c-Fos labelling spread to the cerebral cortex, amygdala, septum and some brainstem regions. With clonic seizures, immunoreactivity was reinforced in all areas already activated by absence-like seizures, and appeared in the striatum, accumbens, brainstem and hippocampus, except in CA1. After SE, c-Fos was strongly expressed in all brain areas. The intensity of c-Fos labelling was higher in most regions of P21 compared to adult rats. These data are in agreement with the immaturity of cellular and synaptic connectivity in P10 rats, the known greater sensitivity of rats to various kinds of seizures during the third week of life and the nature of the neural substrates involved in PTZ seizures.

Aging↗
PubMed1998

[Autosomal dominant nocturnal frontal lobe epilepsy].

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a recently identified seizure disorder. The disease maps to the long arm of chromosome 20 and may be related in some families to a missense mutation in the neuronal nicotinic acetylcholine receptor alpha 4 subunit. We describe one of the first European family with ADNFLE, including five affected individuals spanning four generations. In the most severely affected subject, the onset was during the second month of life and persisted through adult life. Seizures were very frequent during infancy, although long-term evolution was relatively benign. Ictal video-EEG studies showed that attacks occurred in clusters during sleep and were partial seizures that were consistent with a frontal origin. Neuro-imaging was normal. Carbamazepine had a dramatic effectiveness. Although recognition of this syndrome is important for appropriate therapy and genetic counselling, underestimation of cases is likely: the disease was in our family perceived like a hereditary curse, and subsequently concealed, including to medical attention. Relationships with other partial familial epilepsies and with idiopathic benign partial epilepsies of childhood are discussed.

Adult↗
PubMed1997

Effects of pentylenetetrazol-induced status epilepticus on c-Fos and HSP72 immunoreactivity in the immature rat brain.

Pentylenetetrazol (PTZ)-induced status epilepticus (SE) leads to acute and long-term metabolic decreases in specific brain regions of rats at 10 (P10) or 21 days after birth (P21). These decreases are not related to apparent neuronal damage. Therefore, to better understand the neuronal activation and stress response to PTZ in immature rats, we mapped the expression of c-Fos and of the 72 kDa heat-shock protein (HSP72) in the same model of severe SE induced by the repetitive i.p. injections of subconvulsive doses of PTZ. Rats were sacrificed either at 2 or 24 h after the onset of SE in order to reveal c-Fos immunoreactivity, and at 24 and 72 h for HSP72 expression. Hematoxylin-eosin staining was performed at 24, 72 and 144 h after SE. The expression of c-Fos at 2 h after SE was more marked at P21 than at P10 and was prominent at both ages in the hippocampal dentate gyrus, cerebral cortex and amygdala. Some immunoreactivity was also present in the hypothalamus, thalamus and a few brainstem and cerebellar regions at both ages. There was a good relation between the regions expressing c-Fos and those exhibiting acute metabolic decreases at P21. Conversely, PTZ seizures did not lead to any expression of c-Fos at 24 h after SE or of HSP72 at 24 or 72 h at any age. Cell density was not affected by PTZ-induced SE at any age and at any time. These results suggest that c-Fos is a useful marker of neuronal activation induced by severe and prolonged seizures in the immature brain. The lack of HSP72 and of late c-Fos expression likely reflect the absence of neuronal damage in this model of PTZ-induced SE in the immature rat.

Animals↗
PubMed1997

Opposite effects of GABAB receptor antagonists on absences and convulsive seizures.

In Wistar rats with spontaneous non-convulsive absence epilepsy, absence seizures were dose dependently suppressed by intraperitoneal administration of the GABAB receptor antagonists CGP 36742, 50-400 mg/kg, and CGP 56999, 0.25-0.75 mg/kg, and by bilateral microinjections of the same compounds into the lateral nuclei of the thalamus. In rats susceptible to audiogenic seizures, intraperitoneal administration of both GABAB receptor antagonists, at doses which suppressed absence seizures, facilitated the elicitation of sound-induced tonic seizures. In non-epileptic control rats, intraperitoneal injections of higher doses of CGP 36742 (800-2400 mg/kg) and CGP 56999 (3-6 mg/kg) induced delayed clonic convulsions, which were suppressed by pretreatment with baclofen. c-Fos protein was expressed after GABAB receptor antagonist-induced seizures in the cortex, hippocampus, amygdala, perirhinal and piriform cortex. Intra-cortical and hippocampal microinfusion of both GABAB receptor antagonists produced focal seizures. In conclusion, GABAB receptor antagonists suppress non-convulsive absence seizures by blocking thalamic GABAB receptors, while they induce convulsions in cortical and limbic structures.

Animals↗
PubMed1997

Forebrain metabolic activation induced by the repetition of audiogenic seizures in Wistar rats.

In Wistar rats susceptible to audiogenic seizures (Wistar AS) inbred in our laboratory, the exposure to an intense sound induces an epileptic seizure characterized by a running episode followed by a tonic phase showing the major involvement of brainstem structures. After 10-20 sound-induced seizures, development of facial and forelimb clonus and/or tonic-clonic seizures characterize the generalization from brainstem to the forebrain as a result of seizure repetition. In order to specify the anatomical substrates of repeated audiogenic seizures in Wistar AS, we used the 2-deoxyglucose (2DG) technique over a 5 min period to map the midbrain and forebrain structures activated by audiogenic seizures before and after seizure repetition. In naive Wistar AS, six of the 22 structures showed a significant 20-56% increase in relative optical densities compared to non-epileptic controls; these were central and medial amygdala nuclei, perirhinal cortex, medial septum, subthalamic and caudate nuclei. In kindled Wistar AS, 12 additional structures showed a significant 16-121% increase in 2DG labeling. These structures were the substantia nigra, all layers of the hippocampus, the basolateral amygdala, three thalamic nuclei, the frontal motor and prefrontal cortices. In conclusion, the metabolic activation of midbrain and forebrain areas in kindled versus naive Wistar AS rats reflects the changes in the nature of the seizures and the involvement of these structures in the spread of seizure activity from the brainstem to the forebrain during seizure repetition.

Acoustic Stimulation↗
PubMed1997

Binding characteristics of gamma-hydroxybutyric acid as a weak but selective GABAB receptor agonist.

The aim of this study was to reexamine the concept that gamma-hydroxybutyric acid (GHB) is a weak but selective agonist at gamma-aminobutyric acidB (GABAB) receptors, using binding experiments with several radioligands. Ki values of GHB were similar (approximately equal to 100 microM) in three agonist radioligand assays for GABAB receptors, [3H]baclofen (beta-para-chlorophenyl-gamma-aminobutyric acid), [3H]CGP 27492 (3-aminopropyl-phosphinic acid) and [3H]GABA, in the presence of the GABAA receptor agonist isoguvacine with rat cortical, cerebellar and hippocampal membranes. In competition experiments between GHB and the GABAB receptor antagonist, [3H]CGP 54626 (3-N [1-{(S)-3,4-dichlorophenyl}-ethylamino]-2-(S)-hydroxypropyl cyclo-hexylmethyl phosphinic acid), the IC50 values were significantly increased with 300 microM of 5'-guanyl-imidodiphosphate (Gpp(NH)p), which suggested that guanine nucleotide binding proteins (G-proteins) modulate GHB binding on GABAB receptors. The inhibition by GHB of [3H]CGP 27492 binding in cortical membranes was not altered in the presence of 0.3 or 3 mM of the two GHB dehydrogenase inhibitors, valproate and ethosuximide. Thus, GHB is not reconverted into GABA by GHB dehydrogenase. Taken together, the results of this study demonstrated that GHB is an endogenous weak but selective agonist at GABAB receptors.

Animals↗
PubMed1997

Anxiogenic-like consequences in animal models of complex partial seizures.

Several kinds of psychiatric symptoms (anxiety, depression, schizophrenia) have been associated with epilepsies, and clinical data suggest that patients with seizures involving limbic structures are the most prone to develop behavioural disorders between the seizures (i.e. interictally). Studying the neurobiological mechanisms that underlie these symptoms is difficult in humans because of different interfering factors (e.g. psychosocial difficulties, pharmacological side-effects, lesions), which can be avoided in animal models. Using repetitive electrical stimulations (kindling) or local applications of a neuroexcitotoxin in limbic structures (mainly the amygdala and hippocampus), several authors have reported lasting changes of emotional reactivity in cats and rats. These changes appear as anxiety-related reactions expressed as a hyperdefensiveness in the cat, or a reduction of spontaneous exploration in tests predictive of anxiogenic effects in the rat. Some neuroplasticity processes known to develop during epileptogenesis (neuronal-hyperexcitability, modulation of GABA/benzodiazepine transmission) may participate in these lasting changes of behaviour, especially in structures involved in the control of fear-promoted reactions (amygdala, periaqueductal grey matter). In addition, endogenous control systems may also play a critical role in the occurrence of interictal behavioural disorders.

Animals↗
PubMed1997

The amygdala is critical for seizure propagation from brainstem to forebrain.

Audiogenic seizures, a model of brainstem epilepsy, are characterized by a tonic phase (sustained muscular contraction fixing the limbs in a flexed or extended position) associated with a short cortical electroencephalogram flattening. When sound-susceptible rats are exposed to repeated acoustic stimulations, kindled audiogenic seizures, characterized by a clonic phase (facial and forelimb repetitive jerks) associated with cortical spike-waves, progressively appear, suggesting that repetition of brainstem seizures causes a propagation of the epileptic discharge toward the forebrain. In order to determine the structures through which this propagation occurs, four kinds of experiments were performed in non-epileptic rats and in sound-susceptible rats exposed to single or repeated sound stimulations. The following results were obtained: (I) Electrical amygdalar kindling was similar in non-epileptic and naive-susceptible rats, but was facilitated in sound-susceptible rats submitted to 40 acoustic stimulations and presenting kindled audiogenic seizures. (2) Audiogenic seizures induced an increase in [(14)C]2-deoxyglucose concentration in the amygdala after a single seizure, and in the amygdala, hippocampus and perirhinal and piriform cortices after a kindled audiogenic seizure. (3) A single audiogenic seizure induced the expression of c-Fos protein mainly in the auditory nuclei. A few cells were stained in the amygdala. After 5-10 audiogenic seizures, a clear staining appeared in the amygdala, and perirhinal and piriform cortices. The hippocampus expressed c-Fos later, after 40 audiogenic seizures. (4) Injection of lidocaine into the amygdala did not modify single audiogenic seizures, but suppressed myoclonias and cortical spike-waves of kindled audiogenic seizures. Similar deactivation of the hippocampus failed to modify kindled audiogenic seizures. Taken together, these data indicate a critical role for the amygdala in the spread of audiogenic seizures from brainstem to forebrain.

Acoustic Stimulation↗
PubMed1997

Involvement of proprioceptive feedback in brainstem-triggered convulsions.

PURPOSE: In rodents, specific motor components of generalized convulsive seizures depend on two distinct anatomic substrates: (a) forebrain networks are responsible for facial and forelimb clonus with or without rearing and falling; and (b) brainstem networks are responsible for running-bouncing fits and tonic convulsions. To investigate the requirement of proprioceptive inputs in the generation of these two different types of seizures, we compared the effects of neuromuscular blockade by D-tubocurarine on the EEG expression of brainstem- and forebrain-triggered seizures. METHODS: Unilateral electrical stimulations were applied for 50 consecutive days in freely moving male adult rats through a bipolar electrode aimed at the dorsal hippocampus (n = 5), the occipital cortex (n = 4), the inferior colliculus (n = 6), or the midbrain reticular formation (n = 6). Two days after the last stimulation, rats were paralyzed with d-tubocurarine and stimulated in the same way. RESULTS: In brainstem structures, the first electrical stimulation induced tonic seizures concomitant with low-voltage cortical activity; repetition of daily stimulations progressively induced tonic-clonic seizures associated with high-amplitude cortical spike-wave discharges. After immobilization by d-tubocurarine, brainstem stimulations failed to induce any EEG paroxysm. In forebrain structures, repeated electrical stimulations produced a classic kindling with progressive occurrence of clonic seizures associated with large cortical discharges; d-tubocurarine left unchanged the EEG pattern of these latter seizures. CONCLUSIONS: These data suggest that proprioceptive reafferentation resulting from movement is necessary for the generation of self-sustained brainstem seizures but is not implicated in the elaboration of forebrain seizures.

Animals↗
PubMed1997

[Diurnal and nocturnal paroxysmal dyskinesia in young children: a new entity?].

Paroxysmal dyskinesias are intermittent attacks of involuntary hyperkinetics abnormal movements. Among paroxysmal dyskinesias were individualized three entities: paroxysmal kinesigenic choreoathetosis, paroxysmal choreoathetosis of Mount and Reback, hypnogenic paroxysmal dystonia. New classifications are based upon the circumstances of occurrence, the duration of attacks and their etiology. We report here two observations of idiopathic non familial paroxysmal dyskinesias in three-year-old children. Both were seen first in consultation for falls and nocturnal motor agitation. The attacks were paroxysmal jerky "puppet-like" movements lasting from 20 seconds to 15 minutes. They could occur during non REM sleep, during the day, at rest, after a sudden movement, or during prolonged exercise. Carbamazepine was inefficient. These cases were not classifiable according to the classical criteria and could constitute a new entity. Moreover, some sleep-EEG showed abnormal patterns (frontal rapid rhythms, central spikes in one case) and led us to discuss the pathophysiology of this episodic movements disorder, and its relation with frontal partial epilepsy.

Arousal↗
PubMed1997

[GABAergic mechanisms in generalized epilepsies: the neuroanatomical dimension].

Generalized epileptic seizures are underlied by specific circuits where GABAergic synapses are involved at different levels. The role of these synapses depends on (i) the type of epilepsy and (ii) their localization within the central nervous system. This dual complexity can be illustrated by two examples from animal experimentation. Clinical, as well as experimental data have shown that the neural mechanisms underlying generalized non-convulsive seizures (e.g., absence-epilepsy) are distinct from those involved in convulsive generalized seizures. Pharmacological reactivity to anti-epileptic compounds is different between these two forms of seizures. Hippocampus and amygdala are key-structures in convulsive seizures whereas they are not involved in absence-epilepsy. A thalamo-cortical circuit generates the spike-and-wave discharges in absence epilepsy. Global activation of GABAergic transmission by systemic administration generally suppresses convulsive seizures whereas it aggravates absence in both humans and animals. Further investigations using a genetic model of absence seizures in the rat have suggested that this aggravation may be related to the role of post-synaptic GABA-B receptors in slow hyperpolarization, in the relay nuclei of the thalamus. By "de-inactivating" low-threshold calcium currents, activation of these receptors facilitates rhythmic activity in the thalamo-cortical circuit. In addition, regulation of transmitter release by presynaptic GABA-B receptors in the thalamus and the cortex may also contribute to the control of absence seizures. A blockade of the GABA-B receptors, either locally in the thalamus or systemically suppresses absence seizures. The critical role of the substantia nigra in the control of different forms of seizures has been demonstrated recently in the rat. This structure is one of the richest regions of the brain for GABAergic terminals, neurons and receptors. Local applications of GABA mimetics resulting in the desinhibition of their target neurons in the superior colliculus were shown to suppress both convulsive and non-convulsive seizures. This circuitry involving the basal ganglia may exert a "remote inhibitory control" over generalized epilepsies generated in other areas. In conclusion, the pharmacological manipulation of GABAergic transmission has different consequences on epilepsy depending on the form of seizures and the connections and functions of the GABAergic neurons in a given structure. The design of new therapeutical tools based on the manipulation of GABAergic mechanisms in the central nervous system requires to take into account this neuroanatomical dimension.

Animals↗
PubMed1996

Interictal cerebral metabolic levels in Wistar rats sensitive to audiogenic seizures.

In the present study, we compared interictal local cerebral metabolic rates for glucose (LCMRglcs) in a strain of audiogenic rats (Wistar AS) selected in our laboratory to interictal LCMRglcs in a strain of control non-epileptic (NE) rats. Two groups of Wistar AS were studied, one group exposed to a single audiogenic seizure and one group of kindled rats exposed to 40 daily repetitive seizures. Control NE animals were exposed to a single sound exposure which did not induce any behavioral disturbance. Interictal LCMRglcs were measured by the quantitative autoradiographic [14C]2-deoxyglucose technique 5 days after the last sound exposure. LCMRglcs were similar in the three groups of rats in 80% of the structures. Compared to the control NE strain, interictal metabolic levels were mainly decreased in auditory structures of Wistar AS, either naive or kindled, thus confirming auditory impairment in audiogenic animals. LCMRglcs were increased over control levels in both groups of Wistar AS in cerebellar regions. This increase of cerebellar functional activity in Wistar AS compared to control NE rats might reflect an increased cerebellar input which, together with auditory impairment, may facilitate the induction of seizure activity in Wistar AS. Finally, there was no difference between the interictal cerebral metabolic level of naive and kindled Wistar AS, except in the cerebellar dentate nucleus where LCMRglc was significantly higher in kindled than in naive animals.

Acoustic Stimulation↗
PubMed1996

Postencephalitic stereotyped involuntary movements responsive to L-Dopa.

In 1954, at the age of 5 years, our patient had an encephalitic syndrome associated with a prolonged lethargic state. After this episode, he developed a severe parkinsonian syndrome that, after a few years, was associated with axial dystonia and stereotyped abnormal movements of the upper limbs. This complex and progressive extrapyramidal syndrome had many similarities to the encephalitis lethargica as described by von Economo. Results of cerebral computed tomography and magnetic resonance imaging were normal. Fluorodopa positron emission tomography showed a significant bilateral reduction of tracer accumulation in both putamen, similar to that observed in patients with idiopathic Parkinson's disease. However, in this patient, treatment with L-Dopa suppressed all akinetic, dystonic and dyskinetic symptoms. The effectiveness of L-Dopa was abolished by administration of a D2 antagonist and was fully reproduced by a D2 agonist. In conclusion, this patient presented a complex postencephalitic, extrapyramidal syndrome, with akinetic symptoms and involuntary movements. These symptoms appeared to be related to a limited lesion of the dopaminergic neurons of the zona compacta of the substantia nigra.

Adult↗
PubMed1996

Involvement of nigral glutamatergic inputs in the control of seizures in a genetic model of absence epilepsy in the rat.

The reticular part of the substantia nigra is known to be a critical site in the control of epileptic seizures. Potentiation of the direct striatonigral GABAergic projection has been shown to suppress seizures in different animal models of epilepsy. Besides this GABAergic input, the substantia nigra receives glutamatergic inputs, especially from the indirect striatonigral pathway, via the subthalamic nucleus. To investigate the involvement of the nigral excitatory amino acid transmission in the remote control of non-convulsive generalized seizures, several drugs interacting with glutamatergic receptors were first injected into the substantia nigra pars reticulata in rats with spontaneous absence seizures. Blockade of N-methyl-D-aspartate receptors suppressed spontaneous generalized non-convulsive seizures in the rat, whereas blockade of non-N-methyl-D-aspartate receptors was without effect. Second, inhibition of the subthalamic projection by bilateral injections of a GABAergic agonist in this structure similarly suppressed absence seizures. These results suggest that excitatory amino acid inputs are critical in the triggering of the nigral control of generalized epilepsies. Furthermore, they support the hypothesis of a possible involvement of the subthalamonigral pathway in the control of generalized non-convulsive seizures.

Animals↗
PubMed1996

Amygdala kindling in the rat: anxiogenic-like consequences.

Patients with complex partial seizures of temporal lobe origin may experience behavioural disorders like depressive, anxiety-related or schizophrenic-like symptoms between seizures, i.e. interictally. The neural mechanisms underlying these enduring interictal disorders remain to be investigated. The aim of the present study was to examine the behavioural consequences of kindling of the basolateral nuclei of the amygdala, an animal model of limbic complex partial seizures. Animals having experienced 15 stage 5 seizures were compared to non-kindled controls in different behavioural tests performed at least seven days after the last seizure. Kindled animals showed a significant reduction of exploration of open arms in the elevated plus-maze test. In the social interactions test, they showed a decrease of non-social behaviour and an increase of immobility. No modifications were observed in kindled animals when tested in the open field, the sucrose preference or the forced swimming test. The reduction of open arm exploration in the elevated plus-maze was reversed by a pretreatment with chlordiazepoxide (2 mg/kg i.p.), a benzodiazepine anxiolytic. Finally, a similar reduction of open arm exploration was observed when animals were kindled only until a stage 3 seizure occurred. These data, along with previous studies, suggest that kindling of the amygdala has anxiogenic consequences and provide an animal model to study the neuroplasticity phenomena underlying enduring interictal disorders in humans.

Amygdala↗
PubMed1996

Thalamic NMDA transmission in a genetic model of absence epilepsy in rats.

In the selected strain of GAERS Wistar rats (Genétic Absence Epilepsy Rats from Strasbourg), all animals present spontaneously recurrent absence seizures characterized by bilateral and synchronous generalized spike-and-wave discharges (SWD) accompanied by behavioural arrest. SWD depend on a thalamo-cortical network connecting the reticular and relay nuclei of the thalamus and their cortical projection areas. This loop involves both GABAergic and glutamatergic synapses. In the present study, we investigated the implication of NMDA transmission in the genesis of absence seizures in GAERS. Intra-peritoneal or intra-cerebroventricular injections of NMDA, the competitive NMDA antagonist CGP 40116, the non-competitive NMDA antagonist (+)-MK 801 and the antagonist of the glycine modulatory site 5,7-dichlorokynurenic acid dose-dependently suppressed SWD. Bilateral infusions of the same drugs in the lateral relay nuclei of the thalamus had similar suppressive effects. Intra-cerebroventricular or intrathalamic administration of D-serine, an agonist of the glycine modulatory site, had no effect on SWD. These data show that NMDA neurotransmission, especially within the thalamus, plays a major role in the control of absence seizures in GAERs. Disregulation of NMDA-mediated transmission by NMDA or antagonists, interacting with various sites of the receptor complex, may suppress the thalamo-cortical oscillatory activity which underlies SWD.

Animals↗
PubMed1996

Regional differences of the inhibition of GABAB ligand binding by the GTP analogue Gpp(NH)p.

In order to determine whether the interactions between GABAB receptors and G-proteins differ in several brain areas, we have used the reduction in high-affinity GABAB binding by the GTP analogue Gpp(NH)p as an internal assay marker for G-protein linkage to GABAB receptors. The results indicate that Gpp(NH)p inhibits the binding of the GABAB receptor agonist [3H]CGP 27492 (80 to 95%) in a biphasic manner between 0.1 nM and 1 mM. The IC50 for high-affinity sites is significantly higher in cerebellum (70 nM, 53% of binding sites) than in cortex, hippocampus, corpus striatum and thalamus (15-30 nM, 63-73% of binding sites). The IC50S of the low-affinity sites in hippocampus and cortex (170 microM and 210 microM, respectively) were significantly higher than the IC50S in cerebellum, thalamus and corpus striatum (18-39 microM). All these binding sites are sensitive to pertussis toxin (PTX; 7-15 micrograms/mg protein), implicating that they are linked either to Gi or to Gzero proteins. The two binding sites observed (high affinity, nM and low affinity, microM for Gpp(NH)p) and the regional dependence in affinity of these sites may originate either from different GABAB receptor subtypes, different G-proteins or different coupling mechanisms between G-proteins and GABAB receptors. Whereas the PTX site of G-protein linked to GABAB receptors changes with age [24], the GTP binding site does not differ between peripubertal rats (5-6 weeks) and adults rats (10-12 weeks).

Animals↗