The activation of gamma aminobutyric acid(A) receptors in the paraventricular nucleus of the hypothalamus reduces non-contact penile erections in male rats.

Male rats show 4-6 penile erection episodes when put in the presence of an inaccessible receptive female. These non-contact penile erections were reduced dose-dependently by muscimol, a gamma aminobutyric acid (GABA)(A) receptor agonist, when given into the paraventricular nucleus of the hypothalamus (0.1, 0.5, 1 and 2 microg). In contrast, baclofen, a GABA(B) receptor agonist (2 microg) was ineffective. Muscimol reduction of non-contact penile erections was not seen when male rats were pretreated with bicuculline methiodide (2 microg) given 5 min before muscimol into the paraventricular nucleus. Since muscimol injected into the paraventricular nucleus also prevents penile erection induced by drugs (e.g. apomorphine, oxytocin or N-methyl-D-aspartic acid), the present results show that an increased GABAergic activity in the paraventricular nucleus can impair the expression of penile erection induced not only by drugs but also by sexual physiological stimuli.     

PD-168077, a selective dopamine D4 receptor agonist, induces penile erection when injected into the paraventricular nucleus of male rats

The effect of PD-168077 (N-methyl-4-(2-cyanophenyl)piperazynil-3-methylbenzamide maleate), a selective D4 dopamine receptor agonist, injected into the paraventricular nucleus of the hypothalamus on penile erection was studied in male rats. PD-168077 (1-200 ng) induced penile erection in a dose-dependent manner. The minimal effective dose was 50 ng, while the maximal response was found with 200 ng of the compound, which increased penile erection episodes from 0.3+/-0.03 to 1.7+/-0.21. The proerectile effect of PD-168077 was reduced almost completely by L-745,870 (3-(4-[chlorophenyl]piperazin-1-yl)-methyl-1H-pyrrolo[2,3-B]pyridine trihydrochloride), a selective D4 dopamine receptor antagonist, (1 microg) given into the paraventricular nucleus before the D4 dopamine agonist, and by other nonselective dopamine receptor antagonists, such as haloperidol (1 microg) and clozapine (1 microg), which block all dopamine receptor subtypes. The pro-erectile effect of PD-168077 was also reduced by the NO synthase inhibitor NG-nitro-L-arginine methylester (25 microg), but not by the oxytocin receptor antagonist d(CH2)5Tyr(Me)2-Orn8-vasotocin (1 microg), when given into the paraventricular nucleus. In spite of its inability to prevent the pro-erectile effect of PD-168077 when given in the paraventricular nucleus, d(CH2)5Tyr(Me)2-Orn8-vasotocin (1 microg) reduced almost completely PD-168077-induced penile erection when given into the lateral ventricles. The present results show that D4 dopamine receptors present in the paraventricular nucleus may influence penile erection by modulating the activity of paraventricular oxytocinergic neurons mediating erectile function.     

GABA interacts with photic signaling in the suprachiasmatic nucleus to regulate circadian phase shifts

Circadian rhythms of physiology and behavior in mammals are driven by a circadian pacemaker located in the suprachiasmatic nucleus of the hypothalamus. The majority of neurons in the suprachiasmatic nucleus are GABAergic, and activation of GABA receptors in the suprachiasmatic nucleus can induce phase shifts of the circadian pacemaker both in vivo and in vitro. GABA also modulates the phase shifts induced by light in vivo, and photic information is thought to be conveyed to the suprachiasmatic nucleus by glutamate. In the present study, we examined the interactions between GABA receptor agonists, glutamate agonists, and light in hamsters in vivo. The GABA(A) receptor agonist muscimol and the GABA(B) receptor agonist baclofen were microinjected into the suprachiasmatic nucleus at circadian time 13.5 (early subjective night), followed immediately by a microinjection of N-methyl-D-aspartate (NMDA). Both muscimol and baclofen significantly reduced the phase shifting effects of NMDA. Further, coadministration of tetrodotoxin with baclofen did not alter the inhibition of NMDA by baclofen, suggesting a postsynaptic mechanism for the inhibition of NMDA-induced phase shifts by baclofen. Finally, the phase shifting effects of microinjection of muscimol into the suprachiasmatic nucleus during the subjective day were blocked by a subsequent light pulse. These data suggest that GABA regulates the phase of the circadian clock through both pre- and postsynaptic mechanisms.     

An activation of parvocellular oxytocinergic neurons in the paraventricular nucleus in oxytocin-induced yawning and penile erection

Intracerebroventricular (ICV) or PVN local injections of oxytocin induce yawning and penile erection, for which a positive feedback mechanism for the PVN oxytocinergic activation is suggested, but this had not been directly substantiated in vivo. We have assessed the behavioral effects and activity of oxytocinergic neurons with double-staining for c-Fos and oxytocin in the PVN after ICV administration of oxytocin in adult male rats. ICV oxytocin injections (50 and 200 ng) dose-dependently induced yawning and penile erection and significantly increased the percentage of c-Fos positive oxytocin neurons in the medial, dorsal and lateral parvocellular subdivision of the PVN. However, increases in the magnocellular portion were not significant. We also found that lithium chloride (LiCl, 0.5 and l.0 mEq), a compound known to activate oxytocinergic neurons, also significantly increased the percentage of c-Fos positive oxytocin neurons in all PVN portions. However, LiCl did not induce yawning and penile erection, but counteracted the oxytocin-induced yawning and penile erection. These results suggest that if the activation of oxytocinergic neurons in the PVN is important for mediating oxytocin-induced yawning and penile erection, a selective activation of parvocellular oxytocinergic neurons in the PVN is likely to be involved.     

The role of oxytocin and the paraventricular nucleus in the sexual behaviour of male mammals

The paraventricular nucleus of the hypothalamus contains the cell bodies of a group of oxytocinergic neurons projecting to extrahypothalamic brain areas and to the spinal cord, which are involved in the control of erectile function and copulation. In male rats, these neurons can be activated by dopamine, excitatory amino acids, nitric oxide (NO), hexarelin analogue peptides and oxytocin itself to induce penile erection and facilitate copulation, while their inhibition by gamma-aminobutyric acid (GABA) and GABA agonists and by opioid peptides and opiate-like drugs inhibits sexual responses. The activation of paraventricular oxytocinergic neurons by dopamine, oxytocin, excitatory amino acids and hexarelin analogue peptides is apparently mediated by the activation of nitric oxide (NO) synthase. NO in turn activates, by a mechanism that is as yet unidentified, the release of oxytocin from oxytocinergic neurons in extrahypothalamic brain areas. Paraventricular oxytocinergic neurons and mechanisms similar to those reported above are also involved in the expression of penile erection in physiological contexts, namely, when penile erection is induced in the male by the presence of an inaccessible receptive female, which is considered a model for psychogenic impotence in man, as well as during copulation. These findings show that paraventricular oxytocinergic neurons projecting to extrahypothalamic brain areas and to the spinal cord and the paraventricular nucleus play an important role in the control of erectile function and male sexual behaviour in mammals.     

Central control of penile erection: role of the paraventricular nucleus of the hypothalamus

The paraventricular nucleus of the hypothalamus is an integration centre between the central and peripheral autonomic nervous systems. It is involved in numerous functions from feeding, metabolic balance, blood pressure and heart rate, to erectile function and sexual behaviour. In particular, a group of oxytocinergic neurons originating in this nucleus and projecting to extra-hypothalamic brain areas (e.g., hippocampus, medulla oblongata and spinal cord) control penile erection in male rats. Activation of these neurons by dopamine and its agonists, excitatory amino acids (N-methyl-D-aspartic acid) or oxytocin itself, or by electrical stimulation leads to penile erection, while their inhibition by gamma-amino-butyric acid (GABA) and its agonists or by opioid peptides and opiate-like drugs inhibits this sexual response. The activation of these neurons is secondary to the activation of nitric oxide synthase, which produces nitric oxide. Nitric oxide in turn causes, by a mechanism that is as yet unidentified, the release of oxytocin in extra-hypothalamic brain areas. Other compounds recently identified that facilitate penile erection by activating central oxytocinergic neurons are peptide analogues of hexarelin, a growth hormone releasing peptide, pro-VGF-derived peptides, endogenous peptides that may be released by neuronal nerve endings impinging on oxytocinergic cell bodies, SR 141716A, a cannabinoid CB1 receptor antagonist, and, less convincingly, adrenocorticotropin-melanocyte-stimulating hormone (ACTH-MSH)-related peptides. Paraventricular oxytocinergic neurons and similar mechanisms are also involved in penile erection occurring in physiological contexts, namely noncontact erections that occur in male rats in the presence of an inaccessible receptive female, and during copulation. These findings show that the paraventricular nucleus of the hypothalamus plays an important role in the control of erectile function and sexual activity. As the male rat is a model of sexual behaviour and penile physiology, which has largely increased in the last years our knowledge of peripheral and central mechanisms controlling erectile function (drugs that induce penile erection in male rats usually do so also in man), the above results may have great significance in terms of a human perspective for the treatment of erectile dysfunction.     

Electrophysiological actions of the dopamine agonist apomorphine in the paraventricular nucleus during penile erection

The ability to achieve and maintain penile erection is necessary for successful copulation. Studies have demonstrated that dopamine receptor stimulation in the paraventricular nucleus (PVN) of the hypothalamus induces penile erection in rodents, and the dopamine agonist apomorphine has been used to treat erectile dysfunction. The aim of this study was to determine the electrophysiological characteristics of PVN neuronal firing activity in anaesthetised rodents during apomorphine-induced erection. Our findings can be placed in two categories; those effects that occur immediately upon apomorphine administration and continue for up to several minutes prior to penile erection, deemed ‘pre-erectile’, and those effects that were only observed during penile erection and seminal emission. In the pre-erectile period, apomorphine acts on two different populations of PVN neurons to increase or decrease firing rates and increases alpha1 frequency band power in local field potentials. Decreased delta and increased theta frequency power in PVN local field potentials occur only during penile erection and seminal emission. These studies provide further understanding of the coordinated neuronal activity that occurs in the PVN during apomorphine-induced penile erection.     

Cannabinoid CB1 receptors in the paraventricular nucleus and central control of penile erection: immunocytochemistry, autoradiography and behavioral studies

[N-(piperidin-1-yl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxyamide] (SR 141716A), a selective cannabinoid CB1 receptor antagonist, injected into the paraventricular nucleus of the hypothalamus (PVN) of male rats, induces penile erection. This effect is mediated by the release of glutamic acid, which in turn activates central oxytocinergic neurons mediating penile erection. Double immunofluorescence studies with selective antibodies against CB1 receptors, glutamic acid transporters (vesicular glutamate transporters 1 and 2 (VGlut1 and VGlut2), glutamic acid decarboxylase-67 (GAD67) and oxytocin itself, have shown that CB1 receptors in the PVN are located mainly in GABAergic terminals and fibers surrounding oxytocinergic cell bodies. As GABAergic synapses in the PVN impinge directly on oxytocinergic neurons or on excitatory glutamatergic synapses, which also impinge on oxytocinergic neurons, these results suggest that the blockade of CB1 receptors decreases GABA release in the PVN, increasing in turn glutamatergic neurotransmission to activate oxytocinergic neurons mediating penile erection. Autoradiography studies with [(3)H](-)-CP 55,940 show that chronic treatment with SR 141716A for 15 days twice daily (1 mg/kg i.p.) significantly increases the density of CB1 receptors in the PVN. This increase occurs concomitantly with an almost twofold increase in the pro-erectile effect of SR 141716A injected into the PVN as compared with control rats. The present findings confirm that PVN CB1 receptors, localized mainly in GABAergic synapses that control in an inhibitory fashion excitatory synapses, exert an inhibitory control on penile erection, demonstrating for the first time that chronic blockade of CB1 receptors by SR 141716A increases the density of these receptors in the PVN. This increase is related to an enhanced pro-erectile effect of SR 141716A, which is still present 3 days after the end of the chronic treatment.     

Electrical activity and feeding correlates of intracranial hypothalamic injection of GABA, muscimol and picrotoxin in the rats

Assemblies of electrodes and a cannula were stereotaxically implanted in the ventromedial (VMH), lateral (LHA) and paraventricular (PVH) hypothalamic areas in male albino rats. Electrical activity of these regions was recorded electrographically before and following intracranial injection (ICI) of GABA, muscimol and picrotoxin. In another set of animals, food intake and water intake were also measured. The activity of the ventromedial hypothalamus changed from slow to fast after ICI of GABA and picrotoxin and fast to slow after muscimol. The activity of the lateral hypothalamus changed from slow to fast with ICI of muscimol and picrotoxin and from fast to slow with GABA, while that of the paraventricular hypothalamic nucleus changed from slow to fast with ICI GABA and fast to slow with muscimol and picrotoxin. ICI of GABA into VMH and LHA and muscimol in VMH, LHA and PVH caused a decrease in food intake. Water intake was also decreased after ICI of GABA in PVH and muscimol in LHA and PVH. On the opposite picrotoxin increased food intake in VMA and LHA and water intake in PVH. The possible interaction of GABAergic drugs with the areas of the brain controlling feeding and drinking is being discussed.     

Oxytocinergic innervation of autonomic nuclei controlling penile erection in the rat.

In the rat, spinal autonomic neurons controlling penile erection receive descending pathways that modulate their activity. The paraventricular nucleus of the hypothalamus contributes oxytocinergic fibers to the dorsal horn and preganglionic sympathetic and parasympathetic cell columns. We used retrograde tracing techniques with pseudorabies virus combined with immunohistochemistry against oxytocin and radioligand binding detection of oxytocinergic receptors to evidence the oxytocinergic innervation of thoracolumbar and lumbosacral spinal neurons controlling penile erection. Spinal neurons labelled with pseudo-rabies virus transsynaptically transported from the corpus cavernosum were present in the intermediolateral cell column and the dorsal gray commissure of the thoracolumbar and lumbosacral spinal cord. Confocal laser scanning microscopic observation of the same preparations revealed close appositions between oxytocinergic varicosities and pseudorabies virus-infected neurons, suggesting strongly the presence of synaptic contacts. Electron microscopy confirmed this hypothesis. Oxytocin binding sites were present in the superficial layers of the dorsal horn, the dorsal gray commissure and the intermediolateral cell column in both the thoracolumbar and lumbosacral segments. In rats, stimulation of the paraventricular nucleus induces penile erection, but the link between the nucleus and penile innervation remains unknown. Our findings support the hypothesis that oxytocin, released by descending paraventriculo-spinal pathways, activates proerectile spinal neurons.     

Endogenous opioid regulation of stress-induced oxytocin release within the hypothalamic paraventricular nucleus is reversed in late pregnancy: a microdialysis study

Oxytocin secretion into blood in response to swim stress is differentially regulated by endogenous opioids in virgin and pregnant rats. Here, the influence of endogenous opioids on oxytocin release within the hypothalamic paraventricular and supraoptic nuclei was investigated using microdialysis in virgin and pregnant (day 19-21) rats. Rats fitted with a U-shaped microdialysis probe 3 days before testing were injected with naloxone (5 mg/kg body weight, s.c.) or vehicle (sterile saline) and, 3 min later, were forced to swim (10 min at 19 degrees C). Within the paraventricular nucleus, basal and stimulated oxytocin release did not significantly differ between vehicle-treated virgin and pregnant rats. After naloxone, local oxytocin release in response to swimming was lowered in virgin rats (P<0.01), whereas it was further increased in pregnant rats (P<0.01). Within the supraoptic nucleus, basal oxytocin release was significantly lower in pregnant compared to virgin rats (P<0.01). Forced swimming induced a similar rise in intranuclear oxytocin release in both vehicle-treated virgin and pregnant rats, but peak levels were still higher in the virgin controls. In contrast to the paraventricular nucleus, naloxone did not alter swim-induced oxytocin release within the supraoptic nucleus either in virgin or pregnant rats. Vasopressin release in the paraventricular nucleus was also increased by forced swimming but there was no effect of pregnancy or naloxone on it.In summary, in pregnancy, basal and stress-induced oxytocin release within the paraventricular nucleus was not changed, whereas it was blunted within the supraoptic nucleus. Further, within the paraventricular nucleus the excitatory effect of endogenous opioids on local oxytocin release seen in virgins was switched into an inhibitory action in pregnancy. In contrast, endogenous opioids were evidently not involved in the regulation of swim-induced oxytocin release within the supraoptic nucleus either in virgin or pregnant rats. Thus, pregnancy-related neuroendocrine plasticity also includes site-specific functional alterations in opioid receptor-mediated actions in the hypothalamus.     

Gaba(A) receptors in the pedunculopontine tegmental nucleus play a crucial role in rat shell-specific dopamine-mediated, but not shell-specific acetylcholine-mediated, turning behaviour

The role of GABA(A) receptors in the pedunculopontine tegmental nucleus in turning behaviour of rats was studied. Unilateral injection of the GABA(A) receptor agonist, muscimol (25-100 ng), into the pedunculopontine tegmental nucleus dose-dependently produced contraversive pivoting, namely tight head-to-tail turning marked by abnormal hindlimb backward stepping. This effect was GABA(A) receptor specific, since it was prevented by the GABA(A) receptor antagonist, bicuculline (50 ng), which alone did not elicit turning behaviour. Unilateral injection of a mixture of dopamine D(1) ((+/-)-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol [SKF 38393], 5 microg) and D(2) (quinpirole, 10 microg) receptor agonists into the nucleus accumbens shell has been found to elicit contraversive pivoting, whilst unilateral injection of the acetylcholine receptor agonist (carbachol, 5 microg) into the same site is known to elicit contraversive circling, namely turning marked by normal stepping. The pivoting induced by a mixture of SKF 38393 (5 microg) and quinpirole (10 microg) injected into the nucleus accumbens shell was significantly inhibited by bicuculline (50 ng) injected into the pedunculopontine tegmental nucleus, whereas muscimol (25 ng) had no effect. Neither muscimol (25 ng) nor bicuculline (50 ng) modulated the contraversive circling induced by carbachol (5 microg) injected into the nucleus accumbens shell. It is therefore concluded that unilateral stimulation of GABA(A) receptors in the pedunculopontine tegmental nucleus can elicit contraversive pivoting and that the pedunculopontine tegmental nucleus is one of the output stations of the accumbens region that mediates shell-specific, dopaminergic pivoting, but not of the accumbens region that mediates shell-specific, cholinergic circling.     

GABA receptor agonists in the medial preoptic area and maternal behavior in lactating rats

We studied the effects of injecting agonists of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) muscimol (GABA-A receptor agonist) and baclofen (GABA-B receptor agonist) in the medial preoptic area (MPOA) and neighboring brain regions, the bed nucleus of the stria terminalis (BNST), and lateral preoptic area (LPO) on maternal behavior. Lactating female rats were implanted with bilateral cannulae in the MPOA/BNST on day 1 postpartum. On day 5, a maternal behavior test was conducted in the home cage after females received injections of muscimol or baclofen (0, 12.5, 50 or 200 ng per side). On day 7, after MPOA/BNST injections, a second maternal behavior test was conducted with pups placed at the end of a T-runway projecting from the home cage. Finally, after injections on day 9 maternal aggression, olfaction, and locomotor behavior were tested. The GABA receptor agonists injected in the MPOA/BNST produced dose-dependent deficits in all components of maternal behavior, including maternal aggression, except licking. Muscimol produced deficits in the active component, nest building at lower doses than baclofen, both agonists produced deficits in retrieving, while baclofen produced deficits in passive components (hovering and crouching over pups) at lower doses than muscimol. Both GABA receptor agonists increased locomotor activity and reduced olfactory responsiveness but these were only correlated with deficits in retrieving and crouching in baclofen-treated females.     

Role of thalamic gamma-aminobutyrate in motor functions: catalepsy and ipsiversive turning after intrathalamic muscimol

Bilateral intrathalamic microinjections of nanogram amounts (5–50 ng) of muscimol, a γ-aminobutyrate (GABA) receptor agonist, elicited catalepsy in rats. Like neuroleptic-treated rats, those injected with muscimol in the thalamus remained suspended on a vertical grid but, unlike opioid-treated rats, they failed to remain horizontal on two book-holders. The righting reflex was present, while ptosis was absent. The areas with the highest sensitivity to the cataleptogenic effects of muscimol were the ventromedial and ventral-anterior nuclei of the thalamus. These thalamic areas were also characterized by the shortest latency for the induction of catalepsy. Injection of up to 50 ng of muscimol into the caudate, globus pallidus or entopeduncular nucleus failed to produce catalepsy. Catalepsy was also obtained after intrathalamic microinjection of other GABA analogs, such as 3-aminopropanesulphonic and imidazolacetic acid, which are known to be potent GABA receptor agonists, and β-p-chlorophenyl-GABA , a compound which has GABA mimetic activity. The catalepsy produced by 10 ng of muscimol was reversed by an intrathalamic microinjection of picrotoxin, a GABA receptor antagonist. Muscimol-induced catalepsy, unlike neuroleptic-induced catalepsy, was not reversed by systemic administration of high doses of apomorphine, a dopamine receptor agonist, or of scopolamine, a muscarine antagonist, or by intranigral injection of muscimol, and was not prevented by kainic acid-induced lesions of the striatum or of the nigra. Vice versa, injection of cataleptogenic doses of muscimol in the thalamus failed to prevent the stereotyped gnawing produced by systemic apomorphine or intranigral muscimol. Therefore, in these animals, catalepsy and stereotyped gnawing coexisted. The unilateral intrathalamic microinjection of muscimol resulted in a postural asymmetry consisting of turning towards the injected side. This ipsilateral posturing was converted into an ipsilateral circling by systemic administration of apomorphine.The results indicate that thalamic GABAergic mechanisms play an important role in the regulation of posture and in the mediation of certain motor responses arising in the striatum.     

Effects of GABA compounds injected into the subpallidal regions of rat brain on nucleus accumbens evoked hyperactivity

The effects of administration of gamma-aminobutyric acid (GABA) compounds into the ventral pallidum and substantia innominata on the locomotor hyperactivity induced by the dopamine agonist 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN) in the nucleus accumbens were investigated in rats. Hyperactivity induced by ADTN was antagonized by the GABA receptor agonists muscimol, isoguvacine, and baclofen. The compounds were equally effective in both subpallidal regions. In contrast, the GABA antagonists picrotoxin and bicuculline injected into subpallidal sites had no effects on accumbens-evoked hyperactivity, although by themselves both antagonists caused a mild and transient locomotor stimulation. It is suggested that GABA receptors in the subpallidal areas are involved in locomotor stimulation elicited from the nucleus accumbens.     

Ghrelin injected into the paraventricular nucleus of the hypothalamus of male rats induces feeding but not penile erection

The effect of ghrelin, a recently characterized endogenous receptor agonist for growth hormone (GH) secretagogue receptors, on feeding and penile erection was compared with that of EP 80661, a peptide analogue of the GH secretagogue hexarelin, previously identified for its pro-erectile activity when injected into the paraventricular nucleus of the hypothalamus of male rats. Ghrelin (0.01-1 microg), but not EP 80661 (0.02-1 microg), was found to be particularly effective in enhancing feeding. The minimal effective dose of ghrelin was 0.1 microg, which increased food intake by 88%, while the maximal response (355% above control values) was found with 1 microg of the peptide. The enhancing effect of ghrelin on feeding was prevented by the prior administration of the neuropeptide Y Y5 receptor antagonist (DTyr(2), DThr(32)) neuropeptide Y (NPY, 10 microg), but not by the GH-RH receptor antagonist MZ-4-71 (10 microg), or by EP 91073, a hexarelin analogue that antagonizes the pro-erectile effect of EP 80661 (10 microg), given into the lateral ventricles. In contrast, ghrelin failed to induce penile erection at all doses tested, while EP 80661 induced penile erection in a dose-dependent manner. The pro-erectile effect of EP 80661 was prevented by EP 91073 (10 microg), but not by (DTyr(2), DThr(32)) NPY (10 microg) or by the GH-RH receptor antagonist MZ 4-71 (10 microg), given into the lateral ventricles. The present results provide further support to the hypothesis that the GH secretagogue receptors mediating feeding are different from those mediating penile erection and activated by pro-erectile EP peptides.     

Role for GABA agonists in the nucleus accumbens in regulating morphine self-administration

In the present study, functional roles of GABA receptors in the nucleus accumbens on morphine self-administration behavior were investigated. Male Sprague–Dawley rats were trained to press lever for morphine (0.1 mg/kg per infusion) during daily 1-h self-administration session. After establishing stable baseline responses, rats were given microinjections of the GABA_A receptor agonist muscimol (0, 250 and 500 ng/μl, bilateral) or the GABA_B receptor agonist baclofen (0, 100 and 250 ng/μl, bilateral) into the nucleus accumbens immediately before the morphine self-administration. Microinjection of muscimol (250 and 500 ng/μl) into the nucleus accumbens, but not baclofen, decreased morphine self-administration responses. These results suggest that activation of GABA_A receptors, but not GABA_B receptors, in the nucleus accumbens plays a critical role in modulating the reinforcing effects of morphine.     

Augmentation of glutamate responses by GABA in the rat's motorcortex in vivo

The influence of the inhibitory transmitter gamma-aminobutyric acid (GABA) on cortical field potential changes (CFPs) elicited by the excitatory transmitter glutamate and its subreceptor agonists N-methyl-D-aspartate (NMDA) and quisqualate was tested in the motorcortex of anesthetized and artificially ventilated rats. Drugs were applied through a 3-barrelled micropipette by ionophoresis or pressure ejection. Glutamate and its agonists evoked negative and GABA positive CFPs. Applications of GABA before (up to 300 s) the ejection of glutamate, NMDA or quisqualate increased the amplitude of the negative CFP induced by the excitatory transmitters. This augmentation was more pronounced with NMDA and quisqualate than with glutamate. It could be mimicked by the GABAA-agonist muscimol but not by the GABAB-agonist baclofen. It is suggested that the enhancement of glutamate responses by GABA may be mediated by an intracellular common pathway.     

GABAA receptors in the mediodorsal thalamus play a crucial role in rat shell-specific acetylcholine-mediated,but not dopamine-mediated,turning behaviour

The role of GABA_A receptors in the mediodorsal thalamus (mdT) in turning behaviour of rats was studied. Neither the GABA_A receptor agonist muscimol (50 ng) nor the antagonist bicuculline (200 ng) unilaterally injected into the mdT elicited any behavioural change. Unilateral injection of the acetylcholine receptor agonist (carbachol, 5 μg) into the nucleus accumbens shell has been found to elicit contraversive circling while unilateral injection of a mixture of dopamine D₁ ((±)-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol [SKF 38393], 5 μg) and D₂ (quinpirole, 10 μg) receptor agonists into the same site is known to elicit contraversive pivoting. The contraversive circling induced by unilateral injection of carbachol (5 μg) into the nucleus accumbens shell was dose-dependently inhibited by muscimol (25 and 50 ng) injected into the mdT. This inhibitory effect of muscimol (50 ng) was antagonised by co-administration of bicuculline (200 ng), which alone did not modify the contraversive circling induced by carbachol (5 μg). The contraversive pivoting induced by unilateral injection of a mixture of SKF 38393 (5 μg) and quinpirole (10 μg) into the nucleus accumbens shell was inhibited by muscimol (25 and 50 ng) injected into the mdT, whereas bicuculline (200 ng) injected into the mdT did not significantly modify the pivoting. The inhibitory effect of muscimol (50 ng) on the pivoting induced by a mixture of SKF 38393 (5 μg) and quinpirole (10 μg) was not dose-dependent and not antagonised by bicuculline (200 ng). The present study suggests that GABA_A receptors in the mdT play a limited role in spontaneously occurring locomotor activity. Secondly, this study demonstrates that GABA_A receptors in the mdT transmit accumbens-dependent cholinergic circling, but not accumbens-dependent dopaminergic pivoting, to other brain structures. Finally, the present study shows that muscimol-sensitive, non-GABA_A receptors in the mdT influence the accumbens-dependent dopaminergic pivoting. To what extent GABA_B receptors in the mdT mediate the muscimol-induced effects upon the dopaminergic pivoting behaviour requires additional research.     

GABAergic control of food intake in the meat-type chickens

This study examined the effects of intracerebroventricular injections of gamma-aminobutyric acid (GABA) agonists on short-term food intake in meat-type cockerels. In Experiment 1, birds were injected with various doses of muscimol, a GABA(A) agonist. In Experiment 2, the birds received bicuculline, a GABA(A) antagonist, prior to injection of muscimol. In Experiment 3, the effect of varying doses of baclofen, a GABA(B) agonist, on food intake was determined. The intracerebroventricular injection of muscimol caused a dose-dependent increase in food intake. This effect was significantly attenuated by pretreatment with bicuculline. Food intake was not affected by the intracerebroventricular injection of baclofen. These results suggest that GABA acts within the brain of broilers at a GABA(A), but not GABA(B), receptor to increase voluntary food intake.