GABA-induced inactivation of Cebus apella V2 neurons: effects on orientation tuning and direction selectivity

We investigated the GABA-induced inactivation of V2 neurons and terminals on the receptive field properties of this area in an anesthetized and paralyzed Cebus apella monkey. Extracellular single-unit activity was recorded using tungsten microelectrodes in a monkey before and after pressure-injection of a 0.25 or 0.5 M GABA solution. The visual stimulus consisted of a bar moving in 8 possible directions. In total, 24 V2 neurons were studied before and after blocker injections in 4 experimental sessions following GABA injection into area V2. A group of 10 neurons were studied over a short period. An additional 6 neurons were investigated over a long period after the GABA injection. A third group of 8 neurons were studied over a very long period. Overall, these 24 neurons displayed an early (1-20 min) significant general decrease in excitability with concomitant changes in orientation or direction selectivity. GABA inactivation in area V2 produced robust inhibition in 80% and a significant change in directional selectivity in 60% of the neurons examined. These GABA projections are capable of modulating not only levels of spontaneous and driven activity of V2 neurons but also receptive field properties such as direction selectivity.

Role of the caudal pressor area in the regulation of sympathetic vasomotor tone

It is well known that the ventrolateral medulla contains neurons involved in the tonic and reflex control of the cardiovascular system. Two regions within the ventrolateral medulla were initially identified: the rostral ventrolateral medulla (RVLM) and the caudal ventrolateral medulla (CVLM). Activation of the RVLM raises arterial blood pressure and sympathetic nerve activity, and activation of the CVLM causes opposite effects. The RVLM premotor neurons project directly to sympathetic preganglionic neurons and are involved in the maintenance of resting sympathetic vasomotor tone. A significant proportion of tonic activity in the RVLM sympathetic premotor neurons is driven by neurons located in a third region of the ventrolateral medulla denominated caudal pressor area (CPA). The CPA is a pressor region located at the extreme caudal part of the ventrolateral medulla that appears to have an important role controlling the activity of RVLM neurons. In this brief review, we will address the importance of the ventrolateral medulla neurons for the generation of resting sympathetic tone related to arterial blood pressure control focusing on two regions, the RVLM and the CPA.

GABAergic agents modify imipramine analgesia.

The influence of GABA agonists and antagonists on analgesic activity of imipramine (IMA, 20 mg/kg, ip) was studied using the hotplate method. Administration of GABAA receptor agonist muscimol (1 mg/kg, ip), GABAB receptor agonist baclofen (3 mg/kg, ip) or GABA-T inhibitor aminooxyacetic acid (25 mg/kg, ip) increased the analgesic effect of IMA. On the other hand pretreatment of GABAA receptor antagonist bicucukline (2 mg/kg ip), GABAB receptor antagonist delta-amino-n-valeric acid (50 mg/kg, ip) or GABA synthesis inhibitor thiosemicarbazide (50 mg/kg, ip) attenuated the IMA analgesia. These results suggest that the analgesic action of IMA may be mediated by functional alteration of a central GABAergic mechanism and/or subsequent stimulation of GABA receptors.

Inhibitory effects of Diazepam in rat Vas Deferens: role of Calcium

Diazepam and Ro5-4864 effects on noradrenaline-induced rat vas deferend contractions were studied. We investigated whether central or peripheral type benzodiazepine receptors were involved, by studying the effects of the selective central or peripheral benzodiazepine receptor antagonists, flumazenil (Ro 151788) or PK 11195 respectively. Diazepam interactions with GABA, adenosine, theophylline, and hypercalcic medium (3.5mM) were studied. Also, we investigate diazepam effect on KC1 depolarized vas deferens. Results showed that diazepam (10(-4) to 1.7x10(-4) M)) and Ro 5-4864 (10(-5) to 5.5x10(-5)M) inhibited NA-induced vas deferens contractions and that neither flumazenil nor PK 11195 antagonized diazepam or Ro 5-4864 inhibitory effects respectively. GABA, adenosine and theophylline did not modify neither NA vas deferens response nor diazepam inhibitory action. Diazepam effect was significantly reduced in an 3.5 mM calcium medium and KC1 vas deferense was inhibited by diazepam 1.3x10(-5) and 1.3 x 10(-4) M. It is concluded that in rat vas deferens diazepam effect seems to be related with calcium mobilization.

morpho-functional state of the brain under conditions of hypokinesia and its possible pharmacological correction by gaba-ergic substances

In this paper it has been shown that deterioration of the brain cortex capillary system and negative dynamics of cerebral tissue morphology occur under conditions of hypokinesia. Simultaneously, gamma-aminobutyric acid [GABA] and piracetam have been shown to favor the development of vasodilation and prevent further worsening of the cerebral blood supply. During the experiment, it was also established that among the substances investigated, the specific antagonist of GABA-receptors-bicuculline-displays the strongest cerebroprotective effect in early hypokinesia

Effect of manipulation of the GABA system on dopamine-related behaviors

The interaction between GABAergic and dopaminergic system within the central nervous system was investigated in rats using the open-field apparatus and apomorphine-induced stereotypy, and in mice using haloperidol-induced catalepsy. The single intraperitoneal adminsitration of baclofen 3.0 mg/kg, 4,5,6,7-tetrahydroisoxasolo-(5,4-c) piridin-3-ol (THIP) 10.0 mg/kg and picrotoxin 2.0 mg/kg decreased both ambulation and rearing frequencies of the rats in the open-field; only the GABA agonists increased the duration of animal immobility. THIP (10.0 mg/kg) increased the duration of haloperidol-induced catalepsy. For apomorphine-induced stereotypy, baclofen 3.0 mg/kg and picrotoxin 1.0 mg/kg induced a significant leftward displacement of the control dose-response curve constructed for apomorphine (0.1-10 mg/kg) in relation to the control. In addition, baclofen, THIP, picrotoxin and 3-mercaptopropionic acid (3-MPA) 10.0 mg/kg decreased both rearing and sniffing behaviors elicited by apomorphine and increased licking and/ or gnawing. Different mechanisms seem to be involved in the similar effects induced by GABA agonists and antagonists. Picrotoxin induced stereotyped movements per se with a dose-dependent effect, but baclofen and THIP did not. The present data suggest that GABA manipulation facilitates the progressive activation of the different dopaminergic pathways involved in stereotyped behaviors, thus increasing those stereotyped components (gnawing and licking) that appear after a high level of activation of dopaminergic pathways

Effect of GABA modifying agents on seizure susceptibility in insulin hypoglycaemic mice

Insulin hypoglycaemia produced significant catalepsy, reduction in brain GABA content, and enhanced seizure susceptibility as evident by the reduction in the minimal electroshock seizure threshold [MEST]. These effects of insulin were dose-dependent, and were prevented by i. p. treatment with glucose [2 g/kg]. Enhancement of brain GABA content and/or neurotransmission by valproate [300mg/kg] or clonazpam [5 mg/kg] i.p., respectively, prevented the effect of insulin [2U/kg] hypoglycamia on the MEST but potentiated the catalepsy, while depletion of brain GABA content by subconvulsive dose of isoniazid [50 mg/ kg] further enhanced brain excitability in these animals inducing spontaneous convulsion Clonazepam partially corrected the hypoglycaemia, while valproate further reduced the blood glucose level, but isoniazid did not affect it significantly, lt is concluded that the increased seizure susceptibility during hypoglycaemia involves both lack of energy supply to neurones as well as reduction in GABA minergic neuronal inhibition. Clonazepam, and possibly other anticonvulsant benzodiazepines seem to be suitable alternatives to glucose in correcting both these factors, and more preferable to other antiepileptic agents in treating hypoglycaemic convulsions

Effect of GABA modifying agents on electroshock seizure threshold in alloxan diabetic mice

The effect of different Gabaminergic manipulations on the minimal electroshock seizure threshold [MEST] [an index of brain excitability] were studied in alloxan-diabetic mice. Treatment of diabetic mice by clonazepam which potentiates central endogenous GABA neurotransmission, or by valproate which inhibits GABA catabolism, produced a greater rise in MEST than in normal mice. The i.v. injection of gluose in these animals produced marked hyperglycemia associated with increased brain GABA content and MEST. Seizures induced by isoniazid, which inhibits GABA formation, were delayed and attenuated in alloxan-diabetic mice. It is Concluded that diabetic hyperglycemia, partly by enhancing brain GABA formation and turnover, decreases the tendency to seizures and can potentiate anticonvulsants that act largely by Gabaminergic mechanisms