Cardiovascular responses to combined microinjection of substance P and acetylcholine in the intermediolateral nucleus of the rat.

As microinjection of either substance P (SP) or acetylcholine (ACh) into the right intermediolateral cell nucleus (IML) at the T2 level elicits increases in heart rate (HR) in the anesthetized rat, we investigated the possibility of a synergistic effect on HR and arterial pressure (AP) of ACh and SP microinjected in this nucleus. Moreover, we studied the effect on HR and AP of microinjection of either ACh or SP into the IML combined with activation of cardiovascular neurons in the ipsilateral rostral ventrolateral medulla (RVLM) by microinjection of glutamate (Glu). Male Wistar rats (n = 16) were anesthetized with urethane (1.4 g/kg i.p.), artificially ventilated, and the dorsal medulla and spinal cord (T1-T3) were exposed. Micropipettes containing SP and ACh were positioned in the right IML at the T2 level. Microinjection of threshold amounts of ACh (5 x 10(-2) M, 2-10 nl) and SP (3 x 10(-6) M, 2-10 nl) that caused small or no changes in HR or AP (less than 10 bpm or mmHg) elicited statistically significant synergistic increases in HR (22.9 +/- 3.3 bpm) but no changes in AP. Threshold microinjections of Glu (0.18 M, 2-10 nl) into the right RVLM combined with microinjections of threshold amounts of SP or ACh into the ipsilateral IML elicited significant synergistic increases in HR of 13.1 +/- 1.9 bpm and 10.6 +/- 1.9 bpm and in AP of 9.7 +/- 1.9 mmHg and 10.8 +/- 1.7 mmHg, respectively. These results indicate that SP and ACh interact to influence cardioacceleratory spinal preganglionic neurons (SPN) and interact with the transmitter released in the IML by RVLM stimulation to elicit increases in HR.(ABSTRACT TRUNCATED AT 250 WORDS)     

Amphetamine-induced circling behavior in rats: Effects of unilateral microinjections of GABA and GABA-related drugs into substantia nigra

In these experiments, the GABA control upon dopaminergic nigrostriatal neurons has been investigated using circling behavior in the rat. Chronically cannulated rats were givend-amphetamine (2 mg/kg i.p.) 45 min before unilateral microinjection (0.2 μl/2 min) into the substantia nigra (SN) of GABA, muscimol, chlordiazepoxide (CDP) or bicuculline. Circling behavior was continuously recorded for 165 min using an automated rotometer. (1) Non-microinjected control rats exhibit a ‘spontaneous’ circling behavior after amphetamine. (2) When applied to the SN contralateral to the preferential side of the ‘spontaneous’ rotations, saline enhances contraversive circling; GABA (5 × 10⁻⁵M), CDP (5 × 10⁻⁵M) and muscimol (5 × 10⁻⁷M, 5 × 10⁻⁸M) counteract this effect and induce (except CDP) light ipsiversive rotations; GABA (10⁻²M) and muscimol (5 × 10⁻⁵M) further enhance contraversive turning. (3) When applied to the SN ipsilateral to the preferential side of the ‘spontaneous’ rotations, saline has no marked effect on the ipsiversive circling behavior but induces weak contraversive turning; GABA (5 × 10⁻⁵M), CDP (5 × 10⁻⁵M) and muscimol (5 × 10⁻⁸M) enhance the ipsiversive rotations; GABA (10⁻²M) and muscimol (5×10⁻⁵M) transiently decrease the ipsiversive circling; bicuculline (5 × 10⁻⁵M) induces a vigorous contraversive turning associated with a transient inhibition of the ipsiversive rotations. These results suggest that the activity of the nigral neurons is presumably stimulated by the microinjection itself, by bicuculline and, to a lesser extent, by high concentrations of GABA and muscimol, and inhibited by low concentrations of GABA, muscimol and CDP. These findings could further support the hypotheses of a GABAergic inhibitory control upon DA nigrostriatal pathways and of a GABA-like activity of CDP.     

In vivo release of newly synthesized [H]GABA in the substantia nigra of the rat: relative contribution of GABA striato-pallido-nigral afferents and nigral GABA neurons

The release of [3H]gamma-aminobutyric acid ([3H]GABA) continuously formed from [3H]glutamine has been measured with a push-pull cannula implanted in the substantia nigra of the rat anesthetized with ketamine. Consistent with the high density of GABA terminals coming from both the striato-pallido-nigral afferents, and from GABA nigrofugal neurons, our results showed that a large amount of [3H]GABA was spontaneously released in the reticulata, about 4 times higher than in the compacta. In the absence of calcium the spontaneous [3H]GABA release was reduced (-30%), as well as the K(+)-induced release of [3H]GABA (-66%). Bicuculline (10(-4) M) did not affect the K(+)-evoked release of [3H]GABA, suggesting that autoreceptors on GABA afferent fibers are distinct from the GABAA subtype. Partial lesions of striato- and pallido-nigral GABA neurons with kainic acid (1.2 micrograms) decrease by 40% the glutamic acid decarboxylase (GAD) activity in the ipsilateral SN without decreasing the spontaneous release of [3H]GABA; even following extensive lesions with kainic acid (2.5 micrograms), GAD activity (-72%) and spontaneous [3H]GABA release (-83%) were not completely abolished. These results suggest that a non-negligible contribution of GABA nigral neurons accounts for the spontaneous GABA release measured in the substantia nigra. This is further supported by the decrease (-20%), and the increase (+40%) of [3H]GABA release produced by the local application of glycine (10(-6) M), and bicuculline (10(-4) M), which respectively, inhibits and activates the nigral neuron activity. The contribution of nigral GABA neurons to the amount of [3H]GABA release from the substantia nigra, is likely linked to their high spontaneous firing rate.     

GABAergic systems in the nucleus tractus solitarius regulate noradrenaline release in the subfornical organ area in the rat

Previous studies have shown that catecholaminergic neurons in the nucleus tractus solitarius (NTS) with ascending projections to the subfornical organ (SFO) are highly sensitive to gamma-aminobutyric acid (GABA). To clarify the role of the GABAergic system in the NTS in the regulation of the activity of noradrenergic NTS projections to the SFO, the present study was carried out to investigate the effects of local administration (50 nl) of GABA, the GABA(A) agonist muscimol, the GABA(B) agonist baclofen, the GABA(A) antagonist bicuculline or the GABA(B) antagonist phaclofen into the NTS on the release of noradrenaline (NA) in the region of the SFO using microdialysis techniques in rats under urethane anesthesia. Microinjections of GABA (10(-4) - 10(-2) M) into the region of the NTS significantly decreased the NA release in the SFO area. Injections of either muscimol (10(-4) - 10(-2) M) or baclofen (10(-5) - 10(-3) M) into the NTS region significantly attenuated the NA release in the SFO area. Injections of bicuculline (10(-5) and 10(-4) M), but not phaclophen (10(-6) - 10(-4) M), into the NTS region significantly enhanced the NA release in the SFO area, suggesting that the GABAergic system in the NTS may tonically inhibit the NA release in the SFO area through a GABA(A) receptor mechanism. Neither injection of these drugs in any of the doses used in this study into the NTS region caused any significant changes in the NA release in the sites away from the SFO. Injections of vehicle (50 nl) into the NTS region had no significant effect on the NA release in either the SFO area or the sites away from the SFO. These results suggest that the GABAergic system in the NTS may serve to decrease the release of NA in the SFO area and the two types of GABA receptors are involved in the modulation of the NA release.     

Effects of locally infused pharmacological agents on spontaneous and sensory-evoked activity of locus coeruleus neurons

Electrophysiological activity of individual locus coeruleus (LC) neurons was recorded in halothane-anesthetized rats before, during, and after the infusion of adrenergic, cholinergic, or peptidergic compounds about 400 micron lateral to LC. The alpha-adrenergic agonist clonidine (CLON), in concentrations ranging from 5-20 microM (67-270 pg/50 nl injection), reversibly suppressed activity with latencies to onset of 5-15 min and durations of 20-120 min. During the onset of suppressed firing, responses to sensory stimuli (footshock) were relatively preserved, but at later times the reliability of footshock responses was greatly reduced. The alpha-adrenergic antagonist piperoxane (PIP) rapidly reversed the inhibitory effects of CLON. Infusion of 0.1 microliter of 0.02 M acetylcholine (ACh) produced a 3-4 min period of increased LC firing, with a 1 min latency to onset. Larger volumes (0.15 microliter) produced greater increases in firing rate lasting 10-12 min. ACh effects were readily reversed with equimolar doses of scopolamine (SCOP). The effects of 0.02 M ACh were also rapidly reversed by equal volumes of 0.001 M CLON, SCOP and CLON reduced basal firing rates without blocking responses to sensory stimuli. Infusion of the cholinergic agonist carbamyl-beta-choline (carbachol) produced robust, reliable activation of LC neurons at doses of 25-1,000 ng per 100 nl injection. The electrophysiological effects of 3 adrenocorticotropin hormone (ACTH) fragments [1-24], [4-10], and [1-10] were also evaluated. ACTH[1-10] and ACTH[4-10] decreased LC activity for up to 2 hr. ACTH[1-24] exhibited more complex effects, with an increase in discharge rate being accompanied by a decrease in action potential amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of periaqueductal gray on the cardiovascular response evoked by disinhibition of the dorsomedial hypothalamus

Activation of neurons in the region of the dorsomedial hypothalamus (DMH), by microinjection of the GABA(A) receptor antagonist bicuculline methiodide (BMI) results in increases in arterial pressure, heart rate as well as behavioral changes similar to those evoked by acute emotional stress. Previous anatomic studies clearly demonstrated projections from the DMH to the midbrain periaqueductal gray (PAG), a brain region implicated in the organization of behavioral strategies associated with specific cardiovascular responses. In this study, physiological experiments in conscious rats were used to investigate the functional significance of this pathway. Unilateral inhibition of the lateral dorsolateral region of the PAG (l/dlPAG) with the GABA(A) receptor agonist, muscimol (1 nmol/100 nl) largely reduced the tachycardia and the pressor response produced by microinjection of BMI (10 pmol/100 nl) into the ipsilateral DMH. In contrast, inhibition of the ventrolateral PAG (vlPAG) region had no significant effect on the cardiovascular response evoked from disinhibition of the ipsilateral DMH. Our present results indicate that the l/dlPAG region is an important synaptic relay in the descending cardiovascular pathways from the DMH.     

Pentobarbital interaction with the GABA-activated ion channels of the neurons in the rat cerebellum]

GABA and barbiturate-activated currents of isolated single neurons in the rat cerebellum were studied by means of the concentration clamp, voltage clamp and intracellular perfusion methods. The dissociation constant (Kd) was 3 +/- 0.8.10(-5) M. Pentobarbital potentiated the GABA-induced conduction of isolated neurons. The dose-effect for GABA shifted along the abscissa axes. Optimal concentrations which potentiated the GABA effect were within 10(-6)-10(-4) M. The pentobarbital concentrations above 5.10(-4) M without GABA activated the Cl conductance. The short-time conductance during fast pentobarbital washing off was found to increase.     

Features of the chlorine-dependent effect of acetylcholine and neutral amino acids on neurons of the Achatina snail

Responses of neurons in cerebral ganglia of an African giant snail (Achatina fulica) to acetylcholine (ACh), gamma-aminobutyric acid (GABA) and glycine (Gly) were investigated. Cl-dependent currents induced by these mediators in neurons of one and a half month old snail sibs were inhibited by dibutyryl-cAMP and strychnine. Inhibition of ACh-responses by 10(-8) mol/l GABA was mimicked by applications of dibutyryl-cAMP and isobutylmethylxanthine. GABA- and Gly-responses exhibited complete cross-desensitization, but this effect was absent for ACh and GABA (or Gly). On the basis of pharmacological dependences of GABA- and Gly-responses it is suggested that these amino acids act on the same receptor-channel complex in neurons of young snails. ACh-, GABA- and Gly-induced chloride currents were independent in neurons of four years old snails.     

Bilateral asymmetrical changes in the nigral release of [H]GABA induced by unilateral application of acetylcholine in the cat caudate nucleus

In halothane anaesthetized cats, a push-pull cannula was implanted into the right caudate nucleus (CN) and in each substantia nigra (SN). The release of [³H]GABA continuously formed from [³H]glutamine was estimated in each structure. Acetylcholine (ACh, 5 × 10⁻⁵M) added in presence of eserine (5 × 10⁻⁵M) for 50 min in the right caudate nucleus 2 h after the onset of superfusion with [³H]glutamine, stimulated the [³H]GABA release locally. The effect was biphasic when ACh application was made in the median two-thirds of the structure and it was monophasic and transient when the ACh application was restricted to the lateral part. ACH application in the right caudate nucleus also induced changes in [³H]GABA release in the anterior (pars reticulata) and posterior (pars compacta) parts of both SN. While [³H]GABA release was enhanced in the ipsilateral anterior SN, it was reduced in the contralateral anterior SN. Respective opposite effects were observed in the posterior parts of the ipsi- and contralateral SN. These bilateral asymmetrical changes in [³H]GABA release were not dependent on the site of ACh application in the right caudate nucleus. These results indicate that the facilitation of cholinergic transmission in one caudate nucleus influences in an opposite way the striato-nigral GABA neurones on both sides of the brain.     

gamma-Aminobutyric acid inhibits the release of alpha-melanocyte-stimulating hormone from rat hypothalamic slices

The effect of gamma-aminobutyric acid (GABA) on release of alpha-melanocyte-stimulating hormone (alpha-MSH) from hypothalamic neurons was investigated in vitro using the perifusion technique. Rat hypothalamic slices were continuously superfused with Krebs-Ringer medium and the release of alpha-MSH in the effluent perifusate was monitored by means of a sensitive and specific radioimmunoassay method. Infusion of 50 mM K+ for 15 min induced a transient increase of alpha-MSH release (5- to 8-fold above the spontaneous level). Infusion of the same dose of K+ for 75 min caused a brief discharge of alpha-MSH during the first 30 min followed by sustained release of the neuropeptide. The effect of GABA was investigated 27 min after the onset of KCl infusion. Application of GABA (5 x 10(-5) M) resulted in a significant and reversible inhibition of K+-induced alpha-MSH release. The GABAA agonist, muscimol (10(-4) M), produced a prolonged inhibition of K+-evoked alpha-MSH release, while the GABAB agonist, baclofen (10(-4) M), was devoid of effect on hypothalamic alpha-MSH release. Bicuculline (10(-4) M), a specific GABAA antagonist, had no effect when added alone to the medium but totally reversed the inhibitory effect of GABA on K+-induced alpha-MSH release. Taken together, these data suggest that exogenous GABA exerts an inhibitory control on alpha-MSH neurons. Our data also show that the effect of GABA on alpha-MSH release by hypothalamic neurons is mediated through GABAA-type receptors.(ABSTRACT TRUNCATED AT 250 WORDS)     

GABA(A) receptor antagonists enhance cortical acetylcholine release induced by 5-HT(3) receptor blockade in freely moving rats

ACh release from the rat frontal cortex was increased by both local, 0.1-1 microM, and systemic, 0.1-10 microg/kg, administration of the 5-HT(3) receptor antagonist ondansetron, reaching a maximum peak of 143% over basal values. Bicuculline, 1-10 microM, and flumazenil, 5-10 mg/kg, antagonists at different sites of the GABA(A) receptor, also enhanced ACh release, with maximum effects of 85 and 124% above baseline, respectively. GABA(A) receptor antagonists potentiated the effect induced by ondansetron on ACh release, reaching a peak increase of 238% (with bicuculline) and 259% (with flumazenil) over basal levels. These results suggest an interaction of ondansetron with GABAergic neurons modulating ACh release in the rat frontal cortex in vivo.     

Virol A, a toxic trans-polyacetylenic alcohol of Cicuta virosa, selectively inhibits the GABA-induced Cl(-) current in acutely dissociated rat hippocampal CA1 neurons

The effects of virol A (VA), a toxic component of Cicuta virosa (water hemlock), on the GABA-induced Cl(-) current (I(GABA)) in acutely dissociated rat hippocampal CA1 neurons were investigated using whole-cell patch-clamp techniques. VA reversibly reduced I(GABA) and the muscimol (Mus)-induced current (I(Mus)) in a concentration-dependent manner. The IC(50) values for VA against I(GABA) and I(Mus) were 9.6x10(-7) and 9.8x10(-7) M, respectively. VA shifted the EC(50) value of I(GABA) from 6.5x10(-6) to 2.1x10(-5) M, whereas it had no effect on the maximum response, thereby suggesting that VA inhibited I(GABA) in a competitive manner. VA had no apparent effect on current-voltage relationships for I(GABA), thus indicating the lack of voltage-dependency. On the other hand, application of VA (10(-6) M) did not additionally reduce the I(GABA) suppressed by >10(-5) M picrotoxin. VA but not bicuculline accelerated the decay phase of I(GABA), as was seen with picrotoxin. Moreover, pre-application of 10(-5) M VA reduced I(GABA). VA did not inhibit that induced by glycine (10(-4) M). These results indicate that VA inhibits I(GABA) by acting both on the GABA agonist site and on the Cl(-) channel of the GABA(A) receptor-channel complex. VA is a structurally novel type of compound that selectively inhibits the GABA(A) receptor-Cl(-) channel complexes in mammalian central nervous system neurons.     

D1 And D2 Receptors and circling behavior in rats with unilateral lesion of the entopeduncular nucleus

The role of D₁ and D₂ striatal dopamine receptors on circling behavior was studied in a normosensitive model obtained by unilateral kainic acid lesion of the entopeduncular nucleus. In this model, the sensitivity of striatal dopamine receptors was preserved, because kainic acid destroyed the neurons of the entopeduncular nucleus and left undamage the fibers of passage and axon terminals. Systemic administration of SKF 38393 to these animals fails to induce circling activity. In contrast, administration of quinpirole elicited rotation toward the lesioned side, which was increased by concurrent injection of SKF 38393. This behavior was inhibited by pretreatment with either a specific D₁ (SCH 23390) or D₂ (-sulpiride) antagonist. The apomorphine also induced ipsilateral circling that was abolished by pretreatment with D₁ or D₂ antagonists. The above results suggest that coactivation of both D₁ and D₂ striatal dopamine receptors are necessary to induce rotation in this normosensitive model.     

Amyloid beta protein impairs motor function via thromboxane A2 in the rat striatum

Amyloid beta protein (Abeta) deposits are found in the striatum of patients with Alzheimer disease (AD) showing extrapyramidal motor dysfunction, but neuronal cell loss has not yet been detected. To clarify how Abeta impairs motor function, we analyzed intrastriatally Abeta-injected rats. Unilateral injection of Abeta(25-35) enhanced apomorphine-induced circling in an ipsilateral direction, indicating ipsilateral dysfunction of dopaminergic nigrostriatal pathways. Volumes of lesion in the Abeta(25-35)-injected striata were significantly higher than those in the saline-injected ones. The correlation between lesion volume and circling behavior was close to significance, but slightly too low, suggesting the possible involvement of other factors in the striatal dysfunction. Abeta(25-35) significantly elevated the level of thromboxane A2 (TXA2). A stable TXA2 agonist, U46619, enhanced circling behavior, and TXA2 receptor antagonists attenuated U46619- and Abeta(25-35)-enhanced circling behavior. This study demonstrated that Abeta(25-35) impairs the motor function of dopaminergic neurons via neuronal cell loss and TXA2. It also sheds light on the therapeutic potential of TXA2 receptor blockers for the neurotoxicity of Abeta.     

Neurotensin modulation of acetylcholine, GABA, and aspartate release from rat prefrontal cortex studied in vivo with microdialysis

The effects of the peptide transmitter neurotensin (NT) on the release of acetylcholine (ACh), gamma-aminobutyric acid (GABA), glutamate (Glu), aspartate (Asp), and taurine from the prefrontal cortex (PFC) of freely moving rats were studied by transversal microdialysis. Neurotensin (0.2 and 1 microM) administered locally in the PFC produced a concentration-dependent increase in the extracellular levels of ACh, GABA, and Asp, but not of Glu or taurine. The increase produced by 1 microM NT reached a maximum of about 240% for ACh, 370% for GABA, and 380% for Asp. Lower doses of NT (0.05 microM) did not cause a significant change in ACh, GABA, or Asp output in the PFC. Higher concentrations of NT (2 microM) did not induce further increases in the level of neurotransmitters. A high-affinity selective neurotensin receptor (NTR1) antagonist SR 48692 (0.5 microM) perfused locally blocked neurotensin (1 microM)-evoked ACh, GABA, and Asp release. Local infusion of the sodium channel blocker tetrodotoxin (TTX) (1 microM) decreased the release of ACh, had no significant effect on GABA or Asp release, and prevented the 1 microM neurotensin-induced increase in ACh, GABA, and Asp output. Removal of calcium from the Ringer's solution prevented the peptide from having any effects on the neurotransmitters. Thus, in vivo NT plays a modulatory role in the PFC by interacting with cortical neurons releasing GABA and Asp and with ACh-containing neurons projecting to the PFC. The NT effects are of neural origin, as they are TTX-sensitive, and mediated by the NTR1 receptor, as they are antagonized by SR 48692.     

Circling behavior elicited from the pedunculopontine nucleus: evidence for the involvement of hindbrain GABAergic projections

Unilateral microinjection of GABA agonists into the pedunculopontine nucleus (PPN) of the rat resulted in contraversive postural asymmetry and circling behavior; GABA antagonist caused ipsiversive asymmetry and circling when applied to the PPN. A hemitransection was placed immediately caudal to substania nigra (SN) and rostral to PPN in order to interrupt all connections between the PPN and ipsilateral forebrain nuclei. After hemitransection, microinjection of GABAergic drugs into the PPN on the hemitransected side produced postural asymmetry and circling identical to that observed in intact rats. The hemitransection resulted in a loss of glutamic acid decarboxylase activity in PPN (25%) not substantially greater than that observed in animals with unilateral destruction of SN, indicating that a major proportion of GABA terminals in PPN are derived from hindbrain sources. It appears that forebrain (that is, nigrotegmental) GABAergic projections are not essential for the GABA-mediated asymmetry elicited from PPN.     

Resistance to hypoxia in the rat hippocampal slice

Unilateral microinjection of GABA agonists into the pedunculopontine nucleus (PPN) of the rat resulted in contraversive postural asymmetry and circling behavior; GABA antagonists caused ipsiversive asymmetry and circling when applied to the PPN. A hemitransection was placed immediately caudal to substantia nigra (SN) and rostral to PPN in order to interrupt all connections between the PPN and ipsilateral forebrain nuclei. After hemitransection, microinjection of GABAergic drugs into the PPN on the hemitransected side produced postural asymmetry and circling identical to that observed in intact rats. The hemitransection resulted in a loss of glutamic acid decarboxylase activity in PPN (25%) not substantially greater than that observed in animals with unilateral destruction of SN, indicating that a major proportion of GABA terminals in PPN are derived from hindbrain sources. It appears that forebrain (that is, nigrotegmental) GABAergic projections are not essential for the GABA-mediated asymmetry elicited from PPN.     

Involvement of I(1)-imidazoline receptors in baroreceptor reflex in the caudal ventrolateral medulla of rats

There is ample evidence to show the existence of center I(1)-imidazoline receptors that are involved in the regulation of cardiovascular activities. The purpose of this study was to examine the possible role of I(1)-imidazoline receptors and alpha(2)-adrenoceptors within the caudal ventrolateral medulla (CVLM) in mediating the baroreceptor reflex in anesthetized rats. Unilateral microinjection of idazoxan (2 nmol in 50 nl), a mixed antagonist of I(1)-imidazoline receptors and alpha(2)-adrenoceptors, into the CVLM significantly (P<0.01) decreased blood pressure (BP), heart rate (HR), and the firing rate of presympathetic neurons in the rostral ventrolateral medulla (RVLM) by 21+/-6 mmHg, 25+/-5 beats per min and 3.5+/-0.9 spikes/s, respectively. Moreover, unilateral injection of idazoxan into the CVLM significantly (P<0.01) reduced the inhibitory responses of the ipsilateral RVLM presympathetic neurons evoked by stimulation of aortic nerve and elevation of BP, and partially inhibited the neuronal cardiac cycle-related rhythm. Depressor responses evoked by aortic nerve stimulation were significantly (P<0.01) attenuated 10 and 20 min after bilateral microinjection of idazoxan (2 nmol in 50 nl for each side) into the CVLM (-20+/-4 and -30+/-4 vs. -40+/-1 mmHg). However, injection of yohimbine (500 pmol in 50 nl), a selective alpha(2)-adrenoceptor antagonist, into the CVLM did not affect the resting cardiovascular activities and baroreceptor reflex. It is concluded that the CVLM I(1)-imidazoline receptors are involved in maintenance of tonic cardiovascular activities and transmission of the baroreceptor reflex.     

Chemoreceptors for serotonin (5-HT), acetylcholine (ACh), bradykinin (BK), histamine (H) and γ-aminobutyric acid (GABA) on rabbit visceral afferent neurons

The somata of type ‘C’ neurons in rabbit nodose ganglion are endowed with receptor sites for 5-HT, BK, ACh, II and GABA. 5-HT and ACh application to type ‘C’ neurons in the nodose ganglion of rabbits produced a rapid depolarization associated with an increased membrane conductance, most likely to Na⁺ and K⁺. BK and H elicited slow depolarizations accompanied by a decreased membrane conductance probably to K⁺. GABA induced a rapid depolarization associated with an increased conductance to Cl⁻. In contrast, type ‘A’ neurons were insensitive to the four algesic agents but responded to GABA. d-Tubocurarine or picrotoxin at relatively low concentrations blocked ACh, 5-HT and GABA depolarizations without affecting membrane properties. Hexamethonium blocked ACh responses but not 5-HT responses. In addition, no desensitization occurred between the substances 5-HT, ACh or BK. The results suggest that the depolarizing effect of these agents on visceral neurons might be exerted via different receptors.     

Bilateral asymmetrical changes in the nigral release of [3H]GABA induced by unilateral application of acetylcholine in the cat caudate nucleus

In halothane anaesthetized cats, a push-pull cannula was implanted into the right caudate nucleus (CN) and in each substantia nigra (SN). The release of [³H]GABA continuously formed from [³H]glutamine was estimated in each structure. Acetylcholine (ACh, 5 × 10^?5M) added in presence of eserine (5 × 10^?5M) for 50 min in the right caudate nucleus 2 h after the onset of superfusion with [³H]glutamine, stimulated the [³H]GABA release locally. The effect was biphasic when ACh application was made in the median two-thirds of the structure and it was monophasic and transient when the ACh application was restricted to the lateral part. ACH application in the right caudate nucleus also induced changes in [³H]GABA release in the anterior (pars reticulata) and posterior (pars compacta) parts of both SN. While [³H]GABA release was enhanced in the ipsilateral anterior SN, it was reduced in the contralateral anterior SN. Respective opposite effects were observed in the posterior parts of the ipsi- and contralateral SN. These bilateral asymmetrical changes in [³H]GABA release were not dependent on the site of ACh application in the right caudate nucleus. These results indicate that the facilitation of cholinergic transmission in one caudate nucleus influences in an opposite way the striato-nigral GABA neurones on both sides of the brain.