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PubMed1995

GABAA receptor activation induces GABA and glutamate release from preoptic area.

The effect of GABA receptor agonists on release in vitro of radiolabeled GABA and glutamate was studied using a crude preparation of isolated nerve terminals (neurosomes). GABA agonists were incubated (2 min, 37 degrees C) with neurosomes prepared from hypothalamus, preoptic area (POA) and frontal cortex tissues. Under these conditions, GABA and the GABAA receptor agonist muscimol, but not the GABAB receptor agonist baclofen, stimulated 3H-GABA and 3H-glutamate release from POA but not hypothalamic or cortical neurosomes of gonadally intact male rats. These effects were inhibited by the GABAA receptor antagonists picrotoxin, bicuculline and SR-95531. Significant efflux of 3H-glutamate could be elicited from cortical neurosomes following longer (5 min) incubations with 500 microM GABA and 400 microM muscimol. Muscimol-induced release of 3H-glutamate and 3H-GABA was dependent on extracellular calcium. Muscimol and GABA failed to release 3H-GABA or 3H-glutamate from POA neurosomes of ovariectomized female rats. However, administration of estradiol and progesterone to ovariectomized females prior to sacrifice caused the appearance of muscimol induced-release of amino acids from POA neurosomes comparable to that obtained in male rats. GABA-induced release of 3H-glutamate was similarly dependent on pretreatment of ovariectomized rats with ovarian steroids. GABAA receptor-induced release of amino acids is therefore brain region-specific and modified by hormonal status.

Animals↗
PubMed1987

Cardiorespiratory effects produced by injecting drugs that affect GABA receptors into nuclei associated with the ventral surface of the medulla.

It has recently been shown that L-glutamic acid induced stimulation of cell bodies in a circumscribed area of the rostral ventrolateral medulla (RVLM) in the cat, produced increases in arterial pressure (AP), decreases in heart rate (HR) and transient apnea (Gatti, Norman, DaSilva and Gillis, 1986). The purpose of the present study was to determine if this same area was sensitive to GABA receptor agonists and antagonists. Injection of the GABA agonist muscimol (200 ng), into the rostral ventrolateral medulla of cats anesthetized with chloralose produced a precipitous and immediate fall in arterial pressure (-95 +/- 4.6) and heart rate (-31 +/- 5.9; n = 4, P less than 0.05). Maximal cardiovascular effects could only be achieved if muscimol was injected bilaterally. These effects of muscimol on arterial pressure were dose-dependent. Time-action curves for the effects of muscimol on arterial pressure and respiration were different. Hypotension occurred first and was followed later in time by a decrease in minute ventilation. Within 30 min all animals were apneic after the 200 ng dose. The cardiovascular effects of muscimol were reversed by the injection of the GABA receptor antagonist bicuculline. These data indicate that stimulation of GABA receptors in the rostral ventrolateral medulla produced selective cardiovascular effects and that respiratory neurons sensitive to GABA are apparently not localized with these cardiovascular neurons.

Animals↗
PubMed1993

GABAA receptor function in the gamma-hydroxybutyrate model of generalized absence seizures.

gamma-Hydroxybutyric acid (GHB) produces absence-like seizures when given to animals. One of the distinguishing characteristics of experimental generalized absence seizures is that they are exacerbated by GABAA agonists. Therefore, the hypothesis that GHB-induced absence seizures result from an interaction between GHB and the GABAA receptor complex was tested. The effect of GHB on the function of various components of the GABAA receptor complex in the cortex of the rat, was determined in a series of in vitro experiments. Similar studies were carried out at various times following systemic administration of the prodrug of GHB, gamma-butyrolactone (GBL) and changes in the GABAA receptor were correlated with electrographic and behavioral changes. gamma-Hydroxybutyric acid had no effect on the binding of [3H]muscimol, [3H]flunitrazepam and [35S]t-butylbicyclophosphorothionate (TBPS) or on the uptake of 36Cl- into synaptoneurosomes in the in vitro studies. Nor were changes observed after the administration of GBL before the onset of GHB-induced absence seizures. However, at the onset of GHB-induced spike wave discharge, there was a significant (P < 0.04) decrease in the binding of [35S]TBPS, associated with a significant decrease in muscimol-stimulated uptake of 36Cl- with no other biochemical change. One minute after onset of GHB-induced absence seizure, a significant (P < 0.05) increase in the binding of [3H]muscimol was noted. Ten minutes later the decrease in muscimol-stimulated uptake of 36Cl- had normalized, while the changes in binding of [3H]muscimol and [35S]TBPS persisted. Because GABAA function remained unchanged in the in vitro studies, as well as prior to the onset of GHB-induced absence seizures in the in vivo experiments, these studies do not support the hypothesis that GHB interacts directly with the GABAA receptor complex to produce absence-like seizures.

Aminocaproates↗
PubMed1983

Intra-raphe benzodiazepines enhance rat locomotor activity: interactions with GABA.

Intracranial dose response relationships for the water-soluble benzodiazepines, chlordiazepoxide, flurazepam and midazolam, were performed by injecting the drugs through cannulae chronically indwelling in the median raphe nucleus of male albino rats. Drugs were administered in doses of 0.0, 0.22, 0.44, 0.88 and 1.75 nmole in 0.5 microliters saline. Both midazolam and flurazepam produced hyperactivity which was most prominent within the first 30 minutes post-injection. Flurazepam, furthermore, proved twice as potent as midazolam. Chlordiazepoxide, in contrast, was without effect at any of the doses tested. This observation supports the view that chlordiazepoxide is a pro-drug which must be metabolized to form an active metabolite. In another experiment, animals received either saline or a sub-effective dose (0.22 nmole) of flurazepam or midazolam into the median raphe nucleus 5 minutes prior to either a subeffective dose of muscimol (0.22 nmole) or saline. Only the combinations of a benzodiazepine plus muscimol produced hyperactivity. These combinations, moreover, produced effects as robust as those of a 4-fold higher dose of muscimol alone (0.88 nmole). Other animals received either saline or bicuculline methiodide (0.88 nmole). Bicuculline did not affect activity level, but completely blocked the hyperkinetic effects of muscimol. These data suggest that the hyperactivity effect of intra-raphe muscimol is due to activation of GABA receptors within the midbrain raphe, rather than at distant sites. In addition, the data suggest that the intra-raphe administration of certain benzodiazepines produces hyperactivity by facilitating GABA transmission.

Animals↗
PubMed1987

Acute and chronic ethanol treatments alter GABA receptor-operated chloride channels.

The effect of ethanol exposure in vitro on the GABA receptor-operated chloride channel was evaluated by monitoring 36Cl- influx in a membrane vesicle suspension (microsacs) prepared from mouse cerebellum. These experiments directly demonstrate ethanol augmentation of muscimol-stimulated chloride flux. DBA/2J mice were made tolerant to and dependent on ethanol by administration of an ethanol containing liquid diet for 7 days. Exposure to physiologically relevant concentrations of ethanol (10-45 mM) in vitro potentiated muscimol stimulation of 36Cl- uptake in control (pair-fed) membranes, but had no effect on cerebellar microsacs from tolerant/dependent mice. Muscimol stimulation of 36Cl- uptake was not different for pair-fed and ethanol-treated mice. Augmentation of muscimol-induced 36Cl- flux by in vitro ethanol was abolished by a single 4 g/kg injection of ethanol. This "acute tolerance" occurred within 5 min and disappeared within 24 hr after ethanol treatment. The reduced sensitivity of ethanol treated (chronic and acute) mice to ethanol potentiation of muscimol stimulated 36Cl- uptake offers a biochemical correlate to the phenomenon of ethanol tolerance. Moreover, the findings suggest that this biochemical tolerance develops rapidly following a single hypnotic dose of ethanol.

Animals↗
PubMed1987

Noradrenergic rather than GABAergic processes as the common mediation of the antidepressant profile of GABA agonists and imipramine-like drugs in animals.

The present study was aimed at investigating in rats whether a common mechanism might underlie the reversal of depressive-like behaviors by classical antidepressants and by GABA agonists such as muscimol. Blockade of GABA transmission with picrotoxin (1 mg/kg IP) abolished the muscimol (0.5-1 mg/kg)-induced reduction of immobility in the swimming test and the reversal of escape failures in the learned helplessness paradigm. Conversely, picrotoxin was found not to reduce the efficacy of imipramine-like drugs in these same animal models. The combination of muscimol and tricyclics given at subeffective doses resulted in behavioral changes that can be accounted for by an additive interaction between these two classes of drugs. These data confirm the antidepressant-like profile of GABA agonists but suggest that it is unlikely that the primary antidepressant mechanism of conventional antidepressants involves GABA-A receptors. In the swimming test, prazosin (2 mg/kg), an alpha adrenoceptor blocker, antagonized the reduction of immobility produced by both muscimol and imipramine-like drugs. In the learned helplessness paradigm, penbutolol (0.25-0.5 mg/kg) and, though to a lesser extent prazosin, counter-acted the reversal of escape failures caused by muscimol and imipramine. On the basis of these data, it is tempting to speculate that increased transmitter outflow at noradrenergic receptors may be an essential component in the mechanism of action of imipramine-like drugs but also of GABA agonists.

Animals↗
PubMed1993

Biphasic GABA-A receptor-mediated effect on the spontaneous activity of the circular layer in cat terminal ileum.

1. The GABA and GABA-A receptor agonist muscimol changed the spontaneous mechanical activity of a circular layer isolated from cat terminal ileum, while the selective GABA-B receptor agonist (+/-)baclofen had no effect. 2. GABA at doses ranging from 1 microM to 2 mM elicited concentration-dependent biphasic responses which consisted of a relaxation followed by contraction, with a tonic and a phasic component. The EC50 values, calculated at 95% confidence limits (CL), were 94.9 microM (83.5-109.8 microM) and 66.0 microM (51.2-75.5 microM) for the relaxation and contractile phases, respectively. 3. The GABA-induced biphasic responses were sensitive to bicuculline and picrotoxinin and were entirely mimicked by muscimol. Bicuculline competitively antagonized the effects of GABA and gave closely similar pA2 values for both phases of these responses--inhibitory and stimulatory. Cross-desensitization occurred only between GABA and muscimol and not between (+/-)baclofen and GABA, or (+/-)baclofen and muscimol. 4. Both bicuculline-sensitive phases evoked by GABA and muscimol were abolished by tetrodotoxin or atropine, but were unaffected by guanethidine or naloxone. 5. The present results suggested that the biphasic GABA effect on the mechanical activity of the circular layer in cat terminal ileum was mediated by prejunctional GABA-A receptors, most probably through an action on the cholinergic pathway.

Animals↗
PubMed1996

Behavioral changes induced by GABA-receptor agonists in Lymnaea stagnalis L.

1. GABA, the GABAA receptor agonist, muscimol, and the GABAB receptor agonist, baclofen, were tested to study the involvement of the GABA neurotransmitter system in control of behaviour in the freshwater pulmonate snail, Lymnaea stagnalis L. Single injections of GABA (1-10 micrograms/ gbw) into the haemocoel of intact snails elicits a sequence of behavioural changes subsequently affecting feeding, locomotion, escape reactions, male mating behaviour and respiration. 2. Both muscimol and baclofen mimic distinct aspects of GABA action implying that the GABA action is mediated by both types of receptors. 3. The modulatory actions of GABA, muscimol, and baclofen on feeding were manifested as opening of the mouth and triggering of specific radular movements (e.g., protraction, retraction, rasping). 4. Baclofen (1-10 micrograms/gbw) evoked the full erection of the penis for a time long enough for natural copulation, while GABA itself caused only partial eversion of the preputium. Muscimol was less effective than GABA. The latency to penis eversion varied in a dose-dependent manner. The data emphasize the participation of baclofen-sensitive receptors in control of reproduction. 5. GABA and baclofen induced withdrawal of the head and anterior part of the foot accompanied by arrest of locomotion and respiration could be considered to be an escape reaction. 6. Muscimol (1-5 micrograms/gbw) failed to elicit withdrawal reactions but caused the loss of normal orientation and longitudinal contractions of the foot. 7. All the agents tested inhibited locomotion in a dose-dependent manner, for a substantial period of time. A decrease in total locomotor activity lead to the failure of animals to attach to the underlying surface, to have foot contractions and also to diminish locomotor velocity. 8. The majority of animals maintained the stereotyped complex reactions of respiration, but with restricted clockwise turning of the shell after drug treatment. 9. All the substances were shown to shift the background behavioural state characterised by high BSSs to a state similar to "rest" which was awarded a low BSS. It is concluded that the GABA neurotransmitter system can play an important role in activation and coordination of neuronal ensembles underlying behaviour and behaviour selection in Lymnaea stagnalis L.

Animals↗
PubMed1983

Inhibition of drug-induced circling by GABA-ergic activity in the nucleus accumbens.

Injections of GABA (125-500 micrograms in 1 microliter) or muscimol (40-200 ng in 1 microliter) into the nucleus accumbens markedly reduced the amphetamine-induced circling of rats with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of nigrostriatal dopamine neurons. The potency of muscimol was approximately 10(4) times that of GABA. Muscimol exerted a similar effect when injected in a smaller volume (0.5 microliter) at a slower rate (0.11 microliter/min), a procedure which was shown to reduce the spread of injected [3H]muscimol. Intra-accumbens injections of subconvulsive doses of picrotoxin had no effect on amphetamine-induced circling. Intra-accumbens muscimol (40 ng, 0.5 microliter, 0.11 microliter/min) also reduced the contralateral circling evoked by apomorphine in rats with unilateral 6-OHDA-induced lesions of the nigrostriatal pathway and bilateral 6-OHDA-induced lesions of the mesolimbic dopamine terminals. These results suggest that GABA-ergic activity in the nucleus accumbens exerts an inhibitory influence on drug-induced circling. At least part of this action is at a step beyond the release of dopamine from mesolimbic terminals.

Animals↗
PubMed1994

Hypothalamic GABAergic influences on treadmill exercise responses in rats.

Microinjection of GABAergic antagonists in the posterior hypothalamus (PH) produces exercise-like adjustments in cardiovascular function. To test the hypothesis that a hypothalamic GABAergic mechanism within the PH modulates the cardiovascular adjustments to dynamic exercise in conscious animals, Sprague-Dawley rats (n = 10) were instrumented with bilateral guide cannula directed at the pH, an arterial cannula, and Doppler flow probes on the iliac and mesenteric arteries. Saline (100 nl) or the GABAA receptor agonist muscimol (125 ng.100 nl-1) was bilaterally injected into the PH during treadmill exercise (20 m.min-1). Microinjection of saline had no effect on mean arterial pressure (MAP), heart rate (HR), mesenteric vascular resistance (MR), or iliac vascular resistance (IR) during exercise. Microinjection of muscimol during exercise produced no significant changes in MAP (mean change +/- SE; +0 +/- 1 mmHg), HR (+17 +/- 12 b.min-1), or MR (+7 +/- 13%). However, microinjection of muscimol produced a significant increase in IR during exercise (16 +/- 6%). In addition, muscimol significantly decreased treadmill run time (saline = 19.6 +/- 0.4 min; muscimol = 17.8 +/- 0.6 min) and produced behavioral effects (including mild sedation) that were most evident after exercise. The results of these experiments suggest that while the posterior hypothalamic GABAergic system may modulate iliac blood flow during exercise in rats, this system does not modulate HR and MR responses to dynamic exercise.

Animals↗
PubMed1991

Site-specific acylation of GABA-gated Cl- channels: effects on 36Cl- uptake.

Radioligand binding studies indicate that p-isothiocyanato-t-butylbicycloorthobenzoate (p-NCS-TBOB) specifically acylates GABA-gated chloride channels. Preincubation of synaptoneurosomes with p-NCS-TBOB followed by washing resulted in a concentration dependent (63-500 nM) inhibition of both muscimol-stimulated chloride uptake and [355]t-butylbicyclophosphorothionate (TBPS) binding. The extent of acylation (assessed by inhibition of [35S]TBPS binding) was highly correlated (r = 0.89; p less than 0.001) with the inhibition of muscimol-stimulated Cl- uptake. Neither basal Cl- uptake nor [3H]muscimol binding to GABAA receptors were affected by p-NCS-TBOB. Preincubation with the nonacylating 'cage' convulsant t-butylbicycloorthobenzoate (500 nM) followed by washing had no effect on either muscimol-stimulated Cl- uptake or [35S]TBPS binding. These findings indicate that p-NCS-TBOB interferes with the efficacy of muscimol promoted channel openings, but does not affect the recognition qualities of GABAA receptors. p-NCS-TBOB should prove useful in electrophysiological and biochemical studies examining the properties of GABA-gated Cl- channels.

Acylation↗
PubMed2004

GABA(A) receptors in the basolateral amygdala are involved in mediating morphine reward.

In the present study, the effects of intra-basolateral amygdala (BLA) injection of GABA(A) receptor agonist and antagonist on morphine-induced conditioned place preference (CPP) in male Wistar rats have been investigated. Subcutaneous (s.c.) administration of different doses of morphine sulfate (1-9 mg/kg) produced a dose-dependent CPP. Using a 3-day schedule of conditioning, it was found that the GABA(A) receptor agonist, muscimol (0.125, 0.25 and 0.5 microg/rat) or the GABA(A) receptor antagonist, bicuculline (0.125, 0.25 and 0.5 microg/rat), did not produce a significant place preference or place aversion. Intra-BLA administration of muscimol (0.25 and 0.5 microg/rat) decreased the acquisition of CPP induced by morphine (6 mg/kg). On the other hand, intra-BLA injection of bicuculline (0.25 and 0.5 microg/rat) in combination with an ineffective dose of morphine (1 mg/kg) elicited a significant CPP. The response of different doses of muscimol was attenuated by bicuculline (0.125 and 0.25 microg/rat). Furthermore, intra-BLA administration of bicuculline but not muscimol before testing significantly decreased the expression of morphine (6 mg/kg)-induced place preference. The administration of the higher doses of bicuculline (0.25 and 0.5 microg/rat) during acquisition and the higher dose of muscimol (2 microg/rat) on the test day decreased the locomotor activity of the animals on the testing phase. It can be concluded that GABA(A) receptors in the amygdala are involved in morphine reward.

Amygdala↗
PubMed2004

GABAA-5-HT1A receptor interaction in the mediobasal hypothalamus.

Both serotonin (5-HT) and gamma-aminobutyric acid (GABA) modulate female rat lordosis behavior and appear to interact in their control of the behavior. The current experiments were designed to investigate the interaction between these two neurotransmitters in sexually receptive female rats. Ovariectomized female rats, with bilateral cannulae directed toward the ventromedial nucleus of the hypothalamus (VMN), were hormonally primed with 10 microg estradiol benzoate and 500 microg progesterone. Sexual behavior was examined after intracranial infusion with 200 ng (+/-)-8-hydroxy 2-(di-n-propylamino)tetralin (8-OH-DPAT), 25 ng (5-aminomethyl-3-hydroxyisoxazole)hydrobromide (muscimol), 10 ng bicuculline or a combination of the drugs. As expected, 8-OH-DPAT reduced lordosis behavior and muscimol attenuated this inhibition in a bicuculline-sensitive manner. Muscimol alone also reduced lordosis behavior. These findings contrast with several reports that muscimol facilitates lordosis behavior of suboptimally hormonally primed female rats. The current outcome is discussed in terms of procedural differences between the present experiment and earlier studies. It is suggested that muscimol may enhance lordosis responding in suboptimally hormonally primed rats by activation of GABAA receptors located dorsal to the VMN. In contrast, activation of receptors located more ventrally within the mediobasal hypothalamus (MBH) may inhibit the behavior of rats that are already sexually receptive.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2006

GABA(A) receptors of hippocampal CA1 regions are involved in the acquisition and expression of morphine-induced place preference.

In the present study, the effects of bilateral intra-hippocampal CA1 (intra-CA1) injections of GABA(A) receptor agonist and/or antagonist on the acquisition and expression of morphine-induced place preference in male Wistar rats have been investigated. The conditioning treatments with subcutaneous (s.c.) injections of different doses of morphine (0.5-7.5 mg/kg) induced a conditioned place preference (CPP) for the drug-associated place in a dose-dependent manner. Intra-CA1 administration of the GABA(A) receptor agonist, muscimol (0.25, 0.5 and 1 microg/rat) significantly inhibited the morphine (5 mg/kg, s.c.)-induced CPP. Intra-CA1 injections of different doses of the GABA(A) receptor antagonist, bicuculline (0.25, 0.5 and 1 microg/rat), in combination with an ineffective dose of morphine (0.5 mg/kg, s.c.) elicited a significant CPP. However, muscimol or bicuculline by themselves did not elicit any effect on place conditioning. Furthermore, the muscimol-induced inhibition of morphine response was reversed by bicuculline (1 microg/rat, intra-CA1) administration. On the other hand, the bilateral intra-CA1 injections of muscimol (0.25, 0.5 and 1 microg/rat) or bicuculline (0.5, 1 and 2 microg/rat) significantly decreased the expression of morphine-induced CPP. Intra-CA1 administration of different doses of muscimol or bicuculline had no effect on locomotor activity in the testing phase. Our data indicated that the GABA(A) receptors of the hippocampal CA1 regions may play an important role in the acquisition and expression of morphine-induced place preference.

Analysis of Variance↗
PubMed2004

GABAA and GABAB receptors in the nucleus accumbens shell differentially modulate dopamine and acetylcholine receptor-mediated turning behaviour.

The ability of GABAA and GABAB receptors in the shell of the nucleus accumbens to modulate distinct types of turning behaviour was investigated in freely moving rats, using the unilateral injection technique. The GABAA receptor agonist muscimol and the GABAA receptor antagonist bicuculline did not produce turning behaviour; the same holds for the GABAB agonist baclofen and the GABAB antagonist 2-hydroxysaclofen. A mixture of the dopamine D1 receptor agonist SKF 38393 and the dopamine D(2/3) receptor agonist quinpirole has been found to elicit contraversive pivoting, when injected into the shell. This pivoting was dose-dependently inhibited by muscimol, and the inhibitory effect of muscimol was antagonised by bicuculline. Pivoting was also dose-dependently inhibited by baclofen; however, 2-hydroxysaclofen did not antagonise the inhibitory effect. The acetylcholine receptor agonist carbachol has been found to elicit contraversive circling, when injected into the shell. This carbachol-induced circling was inhibited by baclofen, and 2-hydroxysaclofen antagonised the inhibitory effect. Carbachol-induced circling was also partially inhibited by muscimol; however, the inhibitory effect of muscimol was not antagonised by bicuculline. It is concluded that mesolimbic GABAA receptors exert an inhibitory control on dopamine-dependent pivoting that can be elicited from the shell of the nucleus accumbens, and that GABAB receptors exert an inhibitory control on acetylcholine-dependent circling that can be elicited from the shell of the nucleus accumbens. This data extends the earlier reported findings that the neurochemical substrate in the shell of the nucleus accumbens that mediates dopamine-dependent pivoting is fundamentally different from the shell substrate that mediates acetylcholine-dependent circling.

Animals↗
PubMed2006

Enhancement of extinction memory consolidation: the role of the noradrenergic and GABAergic systems within the basolateral amygdala.

Evidence from previous studies indicates that the noradrenergic and GABAergic influences within the basolateral amygdala (BLA) modulate the consolidation of memory for fear conditioning. The present experiments investigated whether the same modulatory influences are involved in regulating the extinction of fear-based learning. To investigate this issue, male Sprague Dawley rats implanted with unilateral or bilateral cannula aimed at the BLA were trained on a contextual fear conditioning (CFC) task and 24 and 48 h later were given extinction training. Immediately following each extinction session they received intra-BLA infusions of the GABAergic antagonist bicuculline (50 ng), the beta-adrenocepter antagonist propranolol (500 ng), bicuculline with propranolol, norepinephrine (NE) (0.3, 1.0, and 3.0 microg), the GABAergic agonist muscimol (125 ng), NE with muscimol or a control solution. To investigate the involvement of the dorsal hippocampus (DH) as a possible target of BLA activation during extinction, other animals were given infusions of muscimol (500 ng) via an ipsilateral cannula implanted in the DH. Bilateral BLA infusions of bicuculline significantly enhanced extinction, as did infusions into the right, but not left BLA. Propranolol infused into the right BLA together with bicuculline blocked the bicuculline-induced memory enhancement. Norepinephrine infused into the right BLA also enhanced extinction, and this effect was not blocked by co-infusions of muscimol. Additionally, muscimol infused into the DH did not attenuate the memory enhancing effects of norepinephrine infused into the BLA. These findings provide evidence that, as with original CFC learning, noradrenergic activation within the BLA modulates the consolidation of CFC extinction. The findings also suggest that the BLA influence on extinction is not mediated by an interaction with the dorsal hippocampus.

Adrenergic beta-Antagonists↗
PubMed2001

Activation of GABA(A) receptors in the amygdala blocks the acquisition and expression of conditioned defeat in Syrian hamsters.

Social defeat is a powerful experience that often leads to drastic physiological and behavioral changes in many animal species. An example of such a change is conditioned defeat in Syrian hamsters. The neurophysiological mechanisms that underlie such changes are not yet fully understood, however, there is evidence that the amygdala plays an essential role in behavioral and emotional responses to a variety of stressors. The goal of the present study was to determine whether GABAergic neurotransmission in the amygdala is a critical component of conditioned defeat in male Syrian hamsters. Experiment 1 examined whether infusion of the GABA(A) receptor agonist, muscimol (0.0, 4.4, 8.8 nmol), into the amygdala would block the acquisition of conditioned defeat. Experiment 2 examined whether infusion of muscimol into the amygdala prior to testing would block expression of conditioned defeat. Submissive behavior during testing was significantly reduced in animals receiving infusions of muscimol immediately prior to initial defeat training. Animals that received infusions of muscimol immediately prior to being tested with a non-aggressive intruder also displayed significantly less submissive behavior than did animals receiving vehicle control. These data indicate that infusion of muscimol into the amygdala can block the acquisition and expression of conditioned defeat, a finding that indicates that GABAergic neurotransmission within the amygdala is involved in the acquisition and expression of fear or stress-induced behavioral changes. This is the first evidence indicating that the neural circuits involved in Pavlovian fear conditioning are also involved in more ethologically-relevant models examining stress-related behavioral plasticity.

Amygdala↗
PubMed2002

GABAergic drugs alter hypothalamic serotonin release and lordosis in estrogen-primed rats.

The effects of muscimol, a GABA(A) agonist, and phaclofen, a GABA(B) antagonist, on serotonin (5HT) release in the mediobasal hypothalamus and lordosis behavior were studied in freely moving rats using in vivo microdialysis. Two days after implantation of bilateral guide cannulae directed towards the ventromedial nucleus of the hypothalamus (VMH), ovariectomized rats were primed with estradiol (E(2)). The rats were implanted with microdialysis probes 24 h later. Following a pretest for lordosis, perfusate 5HT was measured at 20-min intervals until the baseline was stable. The rats were treated with 10, 30 or 100 microM muscimol or 30 and 100 microM phaclofen in artificial CSF delivered via reverse dialysis for 40 min. Control animals were continuously perfused with artificial CSF. Behavior was tested 20, 60 and 180 min after introduction of the drug. Decreased hypothalamic 5HT (40-60% of baseline) and marked facilitation of lordosis were present 20 min after administration of either drug. The effects of 10 and 30 microM muscimol and 30 microM phaclofen on both 5HT and lordosis were reversed after 180 min. Reversal of the behavioral and neurochemical effects were not evident in either the 100 microM muscimol or 100 microM phaclofen groups at the time-points tested. Proceptive responses were observed in phaclofen-treated rats but not in rats treated with muscimol. Levels of hypothalamic 5HT and lordosis quotients in control rats did not significantly differ from initial values. These results suggest that GABAergic effects on lordosis may be mediated through an interaction with 5HT in the mediobasal hypothalamus.

Animals↗