Summary
Functional and neurochemical evidence suggests significant GABA participation in the basomedial hypothalamus. We have investigated electrophysiological effects of GABA using in vitro recording from hypothalamic tissue slices. Exogenous GABA inhibited 94 out of 121 ventromedial hypothalamic (VMN) neurons tested. In sixty-one percent of these GABA-responsive neurons, the inhibitory action of GABA was blocked by GABAA antagonists, bicuculline methiodide (BMI) and picrotoxin (PTX). Nevertheless, many (27/69) GABA-responsive neurons were not sensitive to GABAA blockers: BMI and PTX failed to antagonize inhibitory action of GABA. Most, if it not all, of these inhibitions can be accounted for by GABAB effects, since baclofen powerfully inhibited 42 of 44 neurons tested. In addition to blocking the inhibitory action of exogenous GABA, BMI (55%) and PTX (36%) also caused changes of neuronal activity indicating blockade of intrinsic GABA-ergic action. Altogether, our results showed that, in the VMN, GABA acts through not only GABAA but also GABAB receptors to inhibit neuronal activity, and that there is tonic inhibition by intrinsic GABA neurons. These GABA actions may participate in behaviorallyrelevant VMN hypothalamic mechanisms.
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References
Blume HW, Pittman QJ, Renaud LP (1981) Sensitivity of identified medial hypothalamic neurons to GABA, glycine and related amino acids: influence of bicuculline, picrotoxin and strychnine on synaptic inhibition. Brain Res 209:145–158
Bowery NG, Hudson AL, Price GW (1987) GABAA and GABAB receptor site distribution in the rat central nervous system. Neuroscience 20:365–383
Bowery NG (1989) GABAB receptors and their significance in mammalian pharmacology. TIPS 10:401–407
Carrer HF, Ferreyra H (1980) Anesthetic-dependent excitability changes in the hypothalamic ventromedial nucleus of the rat. Exp Neurol 67:524–538
Donoso AO, Zarate MB (1981) Enhancement of lordotic behavior injection of GABA into the ventromedial nucleus of hypothalamus. IRCS J Med Sci 9:1039
Dreifuss JJ, Matthews EK (1972) Antagonism between strychnine and glycine, and bicuculline and GABA, in the ventromedial hypothalamus. Brain Res 45:599–603
Dutar P Nicoll RA (1988a) Pre- and postsynaptic GABAB receptors in the hippocampus have different pharmacological properties. Neuron 1:585–591
Dutar P, Nicoll RA (1988b) A physiological role for GABAB receptors in the central nervous system. Nature 332:156–158
Enna SJ, Möhler H (1987) γ-aminobutyric acid (GABA) receptors and their association with benzodiazepine recognition sites. In: Meltzer HY (eds) Psychopharmacology: the third generation of progress. Raven Press, New York, pp 265–272
Fernández-Guasti A, Larsson K, Beyer C (1986) Lordosis behavior and GABAergic neurotransmission. Pharmacol Biochem Behav 24:673–676
Frankfurt M, Fuchs E, Wuttke W (1984) Sex differences in γ-aminobutyric acid and glutamate concentrations in discrete rat brain nuclei. Neurosci Lett 50:245–250
Grandison L, Guidotti A (1977) Stimulation of food intake by muscimol and beta endorphin. Neuropharmacology 16:533–536
Kamatchi GL, Bhakthavatsalam P, Chandra D, Bapna JS (1984) Inhibition of insulin hyperphagia by gamma aminobutyric acid antagonists in rats. Life Sci 34:2297–2301
Karlsson G, Pozza M, Olpe H-R (1988) Phaclofen: a GABAB blocker reduces long-duration inhibition in the neocortex. E J Pharmacol 148:485–486
Kelly J, Alheid GF, Newberg A, Grossman SP (1977) GABA stimulation and blockade in the hypothalamus and midbrain: effects on feeding and locomotor activity. Pharmacol Biochem Behav 7:537–541
Kelly J, Rothstein J, Grossman SP (1979) GABA and hypothalamic feeding systems. I. Topographic analysis of the effects of microinjections of muscimol. Physiol Behav 23:1123–1134
Kerr DIB, Ong J, Prager RH, Gynther BD, Curtis DR (1987) Phaclofen: a peripheral and central baclofen antagonist. Brain Res 405:150–154
Kerr DIB, Ong J, Johnston GAR, Prager RH (1989) GABAB-receptor-mediated actions of baclofen in rat isolated neocortical slice preparations: antagonism by phosphonoanalogues of GABA. Brain Res 480:312–316
Kimura H, Kuriyama K (1975) Distribution of gammaaminobutyric acid (GABA) in the rat hypothalamus: functional correlates of GABA with activities of appetite controlling mechanisms. J Neurochem 24:903–907
Kow L-M, Pfaff DW (1984) Neuronal responses to somatosensory and neuropharmacological stimuli in vivo and in vitro: effects of hormonal conditions. In: Bandler R (ed). Modulation of sensorimotor activity during alterations in behavioral states. Alan R. Liss, New York, pp 217–230
Kow L-M, Pfaff DW (1985) Estrogen effects on neuronal responsiveness to electrical and neurotransmitter stimulation: an in vitro study on the ventromedial nucleus of the hypothalamus. Brain Res 347:1–10
Kow L-M. Harlan RE, Shivers BD, Pfaff DW (1985) Inhibition of the lordosis reflex in rats by intrahypothalamic infusion of neural excitatory agents: evidence that the hypothalamus contains separate inhibitory and facilitatory elements. Brain Res 341:26–34
Kow L-M, Pfaff DW (1987) Responses of ventromedial hypothalamic neurons in vitro to norepinephrine: dependence on dose and receptor type. Brain Res 413:220–228
Makara GB, Rappay G, Stark E (1975) Autoradiographic localization of 3H-gamma-aminobutyric acid in the medial hypothalamus. Exp Brain Res 22:449–455
Mandelbrod I, Feldman S, Werman R (1983) The effects of iontophoretic application of putative neurotransmitters on the electrical activity of rat mediobasal hypothalamic neurons in relation to their steroid sensitivity. Brain Res 272:115–127
Mascó D, Weigel R, Carrer HF (1986) Gamma aminobutyric acid mediates ventromedial hypothalamic mechanisms controlling the execution of lordotic responses in the female rat. Behav Brain Res 19:153–162
Matsumoto RR (1989) GABA receptors: are cellular differences reflected in function? Brain Res Rev 14:203–225
McCarthy MM, Malik KF, Feder HH (1990) Increased GABAergic transmission in medial hypothalamus facilitates lordosis but has the opposite effect in preoptic area. Brain Res 507:40–44
Morley JE (1980) The neuroendocrine control of appetite: the role of the endogenous opiates, cholecystokinin, TRH, gammaamino-butyric-acid and the diazepam receptor. Life Sci 27:355–368
Mugnaini E, Oertel WH (1985) An atlas of the distribution of GABAergic neurons and terminals in the rat CNS as revealed by GAD immunohistochemistry. In: Björklund A, Hökfelt T (eds) Handbook fo chemical neuroanatomy, Vol. 4. GABA and neuropeptides in the CNS, Part I. Elsevier, Amsterdam, pp 436–608
Nishizuka M, Pfaff DW (1989) Intrinsic synapses in the ventromedial nucleus of the hypothalamus: an ultrastructural study. J Comp Neurol 286:260–268
O'Connor LH, Nock B, McEwen BS (1988) Regional specificity of gamma-aminobutyric acid receptor regulation by estradiol. Neuroendocrinology 47:473–481
Ogawa S, Kow L-M, Pfaff DW (1988) Effects of GABA antagonists on the electric activity of hypothalamic arcuate (ARC) and ventromedial (VMN) nuclei neurons in vitro. Soc Neurosci Abstr 14:349
Olpe H-R, Steinmann MW, Hall RG, Brugger F, Pozza M (1988) GABAA and GABAB receptors in locus coeruleus: effects of blockers. E J Pharmacol 149:183–185
Pfaff DW, Schwartz-Giblin S (1988) Cellular mechanisms of female reproductive behaviors. In: Knobil E, Neill J et al. (eds) The physiology of reproduction. Raven Press, New York, pp 1487–1568
Sakaue M, Saito N, Taniguchi H, Baba S, Tanaka C (1988) Immunohistochemical localization of γ-aminobutyric acid in the rat pituitary gland and related hypothalamic regions. Brain Res 446:343–353
Soltesz I, Haby M, Leresche N, Crunelli V (1988) The GABAB antagonist phaclofen inhibits the late K+-dependent IPSP in cat and rat thalamic and hippocampal neurons. Brain Res 448:351–354
Stirling JM, Cross AJ, Robinson TN, Green AR (1989) The effects of GABAB receptor agonists and antagonists on potassiumstimulated [Ca2+]i in rat brain synaptosomes. Neuropharmacology 28:699–704
Tappaz ML, Brownstein MJ (1977) Origin of glutamate-decarboxylase (GAD)-containing cells in discrete hypothalamic nuclei. Brain Res 132:95–106
Tappaz ML, Wassef M, Oertel WH, Paut L, Pujol JF (1983) Light- and electronmicroscopic immunocytochemistry of glutamic acid decarboxylase (GAD) in the basal hypothalamus: morphological evidence for neuroendocrine γ-aminobutyrate (GABA). Neuroscience 9:271–287
Wallis CJ, Luttge WG (1980) Influence of estrogen and progesterone on glutamic acid decarboxylase activity in discrete regions of rat brain. J Neurochem 34:609–613
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Ogawa, S., Kow, L.M. & Pfaff, D.W. Effects of GABA and related agents on the electrical activity of hypothalamic ventromedial nucleus neurons in vitro. Exp Brain Res 85, 85–92 (1991). https://doi.org/10.1007/BF00229989
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DOI: https://doi.org/10.1007/BF00229989