Sex differences in the response of rats to drugs affecting GABAergic transmission

Peričić, Danka; Manev, Hari; Lakić, Nela

doi:10.1016/0024-3205(85)90635-6

Cited by 61 publications

(20 citation statements)

References 21 publications

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“…The reports showing the stimu latory effect of picrotoxin and bicuculline [10. 15, 17, 21], as well as the data showing the inhibitory effect of a low dose of diazepam (I mg/kg) on plasma corticosterone level [20,21] are in agreement with the hypothesis that GABA exerts an inhibitory effect on the HHA axis. Since we have shown that two pharmacological antagonists -picrotoxin, a GABA-A receptor blocker [see 3], and high doses of the GABA potentiating drug diazepam both elevate plasma Received: April 20, 1985 Accepted after revision: October 18, 1985 corticosterone level, we were interested in studying the mechanisms involved.…”

supporting

confidence: 75%

“…alters plasma corticosterone level in rats in two different ways [20). High doses of diazepam enhance [16,17,20], while low doses decrease plasma corticosterone levels in nonstressed rats [20,21]. The ability of a high dose of diaze pam to increase plasma corticosterone level in rats has also been reported by other authors [4,12,13,18].…”

mentioning

confidence: 56%

“…It has been shown by us and others that the GABA anta gonist picrotoxin strongly elevates plasma corticosterone level in nonstressed rats [10,15,17,21], supporting the hy pothesis that GABA inhibits the activity of the HHA axis. Neither clonidine nor baclofen affected the picrotoxin-induced rise in plasma corticosterone, indicating that these effects of picrotoxin do not involve alpha-2 or GABA-B re ceptors.…”

Section: Discussionmentioning

confidence: 90%

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Mechanisms by Which Picrotoxin and a High Dose of Diazepam Elevate Plasma Corticosterone Level

1986

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Picrotoxin (1 mg/kg, i.p.) and a high dose of diazepam (10 mg/kg, i.p.) increased the concentration of plasma corticosterone in nonstressed rats. This effect of diazepam was unaffected by picrotoxin and bicuculline (GABA-A receptor blockers), atropine (a muscarinic receptor blocker), apomorphine (a dopamine receptor agonist), haloperidol (a dopamine receptor blocker) and yohimbine (an alpha-2-adrenergic receptor blocker); but was blocked by clonidine (an alpha-2-receptor agonist) and this effect of clonidine was reversed by yohimbine. Diazepam was unable to elevate plasma corticosterone levels in rats pretreated with dexamethasone. Clonidine and the GABA-B receptor agonist, baclofen, failed to affect the picrotoxin-induced rise of plasma corticosterone, but this rise was abolished by a low dose of diazepam (1 mg/kg). The results suggest that the diazepam-induced enhancement of ACTH release, presumably mediated by blockade of alpha-2-adrenergic receptors, is responsible for the observed increase of plasma corticosterone level in rats. On the other hand, the elevation of plasma corticosterone induced by picrotoxin appears to be mediated by GABA-A receptors.

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supporting

confidence: 75%

mentioning

confidence: 56%

Section: Discussionmentioning

confidence: 90%

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Mechanisms by Which Picrotoxin and a High Dose of Diazepam Elevate Plasma Corticosterone Level

1986

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“…Furthermore, previous findings in our laboratories have shown that GABA A receptor subunits are found in the majority of PeN SRIH cells [18]. GABA has also been implicated in the generation of sex differences in several brain regions [19, 20], including the GnRH neurons of the hypothalamus [21], and many hypothalamic GABAergic neurons express estrogen receptors [22]. Thus, changes in the steroid environment alter levels of GABA, the enzymes involved in its synthesis and degradation and receptor subunit expression [22, 23, 24, 25, 26].…”

Section: Introductionmentioning

confidence: 99%

Sexually Dimorphic Ontogeny of GABAergic Influences on Periventricular Somatostatin Neurons

Murray

Rantle²,

Simonian³

et al. 1999

Neuroendocrinology

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The biosynthesis and secretion of somatostatin (SRIH) within the hypothalamic periventricular-median eminence (PeN-ME) pathway follows a sexually differentiated developmental pattern beginning in the early neonatal period. It is generally accepted that testosterone plays a role in these processes, but the mechanisms underlying the age and sex differences are poorly understood. The present study sought to investigate the hypothesis that γ-aminobutyric acid (GABA) may play a role in determining sex differences in SRIH neuronal activity. Using an in vitro hypothalamic preparation where more than 97% of the immunoreactive SRIH is contained within the PeN-ME pathway, peptide release in response to the GABA_A receptor antagonist, bicuculline, was followed through development. In the male a stimulatory response, indicative of an inhibitory GABAergic tone on SRIH secretion, was observed as early as postnatal day (P) 5. This persisted throughout juvenile development (P10, P17) and was present also in the adult male (P75), but in the peripubertal period the response to bicuculline was first lost (P25) and then reversed to an inhibition (P40), suggesting a transient switch to an apparent stimulatory GABAergic tone on SRIH release. By contrast, in the female, no bicuculline responsiveness was seen until P25 when it caused a decrease in SRIH release which persisted into adulthood. Using in situ hybridization studies we found no evidence to support the view that these age- and sex-dependent differences were due to changes in the expression of GABA_A receptor α-subunits (α₁ and α₂) which are colocalised in the PeN SRIH neurons. Following adult gonadectomy, the bicuculline response was abolished in the male, whereas, in the female it was reversed and identical in magnitude to the response in the intact male. These results demonstrate marked sex differences in GABA_A-receptor-mediated influences on SRIH release which develop soon after birth and, in the adult, depend on gonadal factors. In the male these factors activate a primarily inhibitory influence, whereas in the female they facilitate an apparently stimulatory tone of GABA on SRIH secretion via the GABA_A receptor. Our findings thus support the view that GABAergic transmission may play a key role in generating sex differences in the mode of SRIH secretion from the hypothalamus which has been shown to be a major factor in determining the sexually dimorphic patterns of growth hormone secretion.

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“…Earlier studies have shown sex differences in the response of rats to drugs affecting GABAergic transmission (35)(36)(37). These authors suggested that the sex difference observed was due to a difference among the sexes in GABA system activity.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Inhibitory Effect of Oestradiol on Functional GABA/5‐HT Relationship in the Rat Suprachiasmatic Area

François‐Bellan¹,

Héry²,

Faudon³

et al. 1989

J Neuroendocrinology

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The purpose of this study was to test the capacity of oestradiol to modulate the stimulating effect of a-aminobutyric acid (GABA) on serotonin (5-HT) metabolism, previously described in the suprachiasmatic area of the male rat. After an in vivo stimulation of GABA transmission by systemic administration of a GABA-transaminase inhibitor (amino-oxyacetic acid) or a GABA, agonist (RS-baclofen), the 5-HT metabolism was studied in the suprachiasmatic area of ovariectomized, and ovariectomized oestradiol-treated rats.Amino-oxyacetic acid or RS-baclofen treatment increased the endogenous content of 5-HT in the suprachiasmatic area of males and ovariectomized rats. These two treatments were without effect in ovariectomized oestradiol-treated rats. GABA transmission stimulation induced by amino-oxyacetic acid treatment failed to affect the release and synthesis of 5-HT in ovariectomized oestradiol-treated rats while it increased these two parameters of 5-HT metabolism in the suprachiasmatic area of male and ovariectomized rats. To investigate the main target of oestradiol effect, comparative studies of the serotoninergic and GABAergic metabolism in the suprachiasmatic area were performed in the three experimental groups. Under our experimental conditions the endogenous 5-HT metabolism was similar between ovariectornized and ovariectomized oestradiol-treated rats. Nevertheless, 5-HT metabolism was higher in the two female groups than in the male group. Neither GABA metabolism nor GABAergic response to GABA-related drug treatment differed between ovariectomized, and ovariectomized oestradiol-treated rats. However, the turnover of GABA was higher when compared to the two female groups. It is concluded that the lack of 5-HT responsiveness to GABA transmission stimulation in ovariectomized oestradiol-treated rats was not related to an effect of oestradiol on 5-HT metabolism or to an effect of the steroid on GABA turnover. Furthermore, our results suggest a sex difference in the activity of serotoninergic and GABAergic systems in the suprachiasmatic area.Recently, an anatomical relationship between GABAergic and szrotoninergic terminals in the suprachiasmatic nucleus (SCN) has been reported (1). Parallel to previous reports we have shown the existence of a metabolic interaction between these two neurotransmitters. The stimulation of y-aminobutyric acid (GABA) transmission leads to an increase in serotonin (5-HT) metabolism la GABA, receptor activation in the rat's suprachiasmatic area (SCA) (2, 3). The ability of oestradiol (E,) to influence neurotransmission has long been recognized. There are numerous (4-6) examples of mechanisms by which E, may act on neurotransmitter systems. These include the modulation of neurotransmitter metabolism and effects on neurotransmitter receptor concentrations. Data concerning the effects of the steroid on 5-HT and GABA metabolism in the hypothalamus are conflicting. While some authors report that E, administration to ovariectomized animals (OVX) results in no change in 5-HT content of...

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Sex differences in the response of rats to drugs affecting GABAergic transmission

Cited by 61 publications

References 21 publications

Mechanisms by Which Picrotoxin and a High Dose of Diazepam Elevate Plasma Corticosterone Level

Mechanisms by Which Picrotoxin and a High Dose of Diazepam Elevate Plasma Corticosterone Level

Sexually Dimorphic Ontogeny of GABAergic Influences on Periventricular Somatostatin Neurons

Analysis of the Inhibitory Effect of Oestradiol on Functional GABA/5‐HT Relationship in the Rat Suprachiasmatic Area

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