The effects of baclofen on calcium channel currents in dorsal sensory cells of the spinal cord in the lamprey

Dorsal sensory cells isolated from the spinal cord of the lamprey speciesIchthyomyzon unicuspis andLampetra fluviatilis were used for whole-cell patch-clamp studies of the effects of baclofen on calcium channel currents, evoked in conditions in which Na⁺, K⁺ currents were blocked, by depolarizing membranes from constant holding potentials of −100 or −80 mV to +30 mV. Ba ions were used as carriers of currents through calcium channels. These studies demonstrated that baclofen (0.5 mM) decreased the peak amplitude of the Ba²⁺ current by an average of 22.5±4.2% (n=12) in dorsal sensory cells of the lampreyIchthyomyzon unicuspis and by 28.4±3.3% in the dorsal sensory cells ofLampetra fluviatilis (n=25). The conductivity of dorsal sensory cell membranes in the presence of baclofen (and GABA) did not change. The blocking action of baclofen persisted in the presence of bicuculline (100 μM) and was lifted by addition of δ-aminovaleric acid and 2-hydroxysaclofen to the perfusing solution. These results are interpreted as evidence for the presence of GABA_B receptors in dorsal sensory cell membranes. The data were compared with published results, and the question of the functional significance of GABA_B receptors in the dorsal sensory cells (primary afferent cells) of cyclostomata is discussed. Translated from Rossiiskii Fiziologischeskii Zhurnal imeni I. M. Sechenova, Vol. 83, No. 11-12, pp. 92–104, November–December, 1997.     

Effect of bilateral destruction of the subretrofacial area on receptor mechanisms of neuroprotective effect of GABAergic agents

Both GBA_A (muscimol, gaboxadol, and isonipecotate) and GABA_B (baclofen) receptor agonists produce marked neuroprotective effect during total brain ischemia. The antagonists of GABA_A receptors bicuculline and picrotoxin attenuate the effect of muscimol, and the GABA_B receptor antagonists hydroxysaclofen and aminovaleriate decrease the effect of baclofen. The GABAergic substances protect the brain via GABA receptors of both types. The effect of the GABA agonists is central in nature. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 2, pp. 162–164, February, 1998.     

Additivity and independence of neuroprotective effects of GABAA and GABAB receptor agonists in complete global cerebral ischemia

Neuroprotective effects of GABA_B agonist baclofen and GABA_A agonists THIP and muscimol are completely additive. GABA_A and GABA_B receptor antagonists block the neuroprotective effects of the corresponding agonists without cross-blocking. In fact, the blockade of combined effect of two agonists with selective GABA_A and GABA_B antagonists separately and in combination is not below the estimated value. Therefore, GABA_A and GABA_B receptor mechanisms of the neuroprotective effects independently and separately contribute to the improvement of brain resistance to global ischemia. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 130, No. 8, pp. 187–189, August, 2000     

Additivity and independence of neuroprotective effects of GABAA and GABAB receptor agonists in complete global cerebral ischemia

Neuroprotective effects of GABA_B agonist baclofen and GABA_A agonists THIP and muscimol are completely additive. GABA_A and GABA_B receptor antagonists block the neuroprotective effects of the corresponding agonists without cross-blocking. In fact, the blockade of combined effect of two agonists with selective GABA_A and GABA_B antagonists separately and in combination is not below the estimated value. Therefore, GABA_A and GABA_B receptor mechanisms of the neuroprotective effects independently and separately contribute to the improvement of brain resistance to global ischemia. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 8, pp. 187–189, August, 2000     

Rhythmical bursting activity and GABAergic mechanisms in the medial septum of normal and pertussis toxin-pretreated rats

Summary The possible involvement of GABA in the control of the rhythmical bursting activity (RBA) of septo-hippocampal neurons (SHNs) has been studied in the rat in vivo. The discharge frequency of SHNs was modified by the iontophoretic application of a GABA agonist and antagonist as well as by the application of the GABA uptake blocker, nipecotic acid. The GABA_B agonist baclofen inhibited the SHNs' activity, this effect being antagonized by the GABA_B antagonist phaclofen. However, these different pharmacological manipulations did not modify the RBA frequency. Pretreatment of the rats with pertussis toxin, a substance which is known to block the events mediated by G-proteins (Gi or Go), decreased the RBA frequency. Neither agonists nor antagonists of GABA_A or GABA_B types had significant effects on the rhythmical bursting activity of SHNs. The effect of pertussis toxin suggests that other neurotransmitters or intrinsic mechanisms involving a G-protein influence this rhythm.     

Proton inhibition of GABA-activated current in rat primary sensory neurons

 The modulation of the Cl^– current activated by γ-aminobutyric acid (GABA) by changes in extracellular pH in freshly isolated rat dorsal root ganglia (DRG) neurons was studied using the whole-cell patch-clamp technique. In the pH range of 5.0–9.0, increased extracellular pH enhanced, and decreased extracellular pH suppressed, current activated by 10 μM GABA in a reversible and concentration-dependent manner with an IC₅₀ of pH 7.1 in these neurons. Acidification to pH 6.5 inhibited currents activated by the GABA_A-selective agonist muscimol in all neurons tested. The antagonism of GABA-activated current by lowering the pH was equivalent at holding potentials between –80 and +40 mV and did not involve a significant alteration in reversal potential. Acidification shifted the GABA concentration/response curve to the right, significantly increasing the EC₅₀ for GABA without appreciably changing the slope or maximal value of the curve. Inhibition of the GABA-activated current by protons was not significantly different when the patch-pipette solution was buffered at pH 7.4 or pH 6.5. These results suggest that extracellular protons inhibit GABA_A receptor channels in primary sensory neurons by decreasing the apparent affinity of the receptor for GABA. This represents a novel mechanism of inhibition by protons of a neurotransmitter-gated ion channel. Proton inhibition of GABA_A receptor channels may account in part for the modulation by protons of sensory information transmission under certain pathophysiological conditions. Received: 1 July 1997 / Received after revision: 29 September 1997 / Accepted: 15 October 1997     

Effects of inhibitory neurotransmitters on the mudpuppy (Necturus maculatus) locomotor pattern in vitro

Effects of inhibitory neurotransmitters on the locomotor rhythm and pattern generation were investigated using an in vitro preparation isolated from the mudpuppy (Necturus maculatus). The preparation consisted of the first five segments of the spinal cord and the right forelimb attached by the brachial nerves. During N-methyl-d-aspartate (NMDA)-induced locomotion, the rhythmic motor output (EMG) was recorded unilaterally from elbow flexor and extensor muscles. While neither glycine nor γ-aminobutyric acid (GABA)-related substances induced locomotion in the absence of NMDA, they modulated NMDA-induced locomotion. Bath application of glycine and GABA suppressed the rhythmic motor pattern induced by NMDA. Addition of glycine receptor antagonist strychnine or GABA_A receptor antagonist bicuculline disrupted the phase relationship between antagonistic motor pools during ongoing locomotion, thereby changing the normal alternating pattern into synchronous EMG bursts. Both the GABA_A receptor agonist muscimol and GABA_B receptor agonist baclofen mimicked the effects of GABA as they either slowed down or stopped locomotion. Nipecotic acid, a GABA uptake blocker, had a similar effect. This suggested that an endogenous release of GABA modulated the locomotor rhythm. The endogenous release was antagonized by the GABA_A and GABA_B receptor antagonists bicuculline and CGP-35348, respectively. Immunocytochemistry revealed that glycine and GABA-positive neurons and fibers were present in mudpuppy spinal cord. Although the GABAergic neurons were more numerous than glycinergic neurons, both cell types contributed processes directed towards the white matter and occasionally towards the ependymal lining of the central canal. Our results suggest that inhibitory neurotransmitters exert powerful actions upon the neuronal network governing forelimb locomotion in the mudpuppy. The effects we observed may be mediated by a network of segmentally distributed glycinergic and GABAergic spinal neurons. Received: 1 December 1998 / Accepted: 26 April 1999     

Effects of intracellular calcium on GABAA receptors in mouse cortical neurons

 Using the patch-clamp technique, we studied the effect of intracellular Ca²⁺ on Cl^– current gated by type A γ-aminobutyric acid receptors (GABA_A) in mouse cortical neurons. When the rapid Ca²⁺ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid (BAPTA) was in the pipette solution, the GABA-activated Cl^– current amplitude decreased over time to 49 ± 7% of control. In contrast, equimolar replacement of BAPTA with ethylenebis(oxonitrilo)tetraacetate (EGTA) caused a 60 ± 10% increase in GABA current. An increased intracellular Ca²⁺ concentration caused a transient augmentation of the GABA current. This effect of Ca²⁺ was concentration dependent (10 nM to 34 μM). Ca²⁺ increased the amplitude of the current by enhancing the maximal response to GABA rather than by changing the affinity of the receptor to GABA (EC₅₀ = 5 ± 0.4 μM vs. 7 ± 0.3 μM). Both calmodulin (CaM) and a CaM kinase II inhibitor (200 μM) blocked the potentiating effect of Ca²⁺ suggesting that it was mediated by activation of CaM kinase II. We found that regulation of GABA_A receptors by intracellular Ca²⁺ in cortical neurons has important physiological implications since the potentiating effect of increasing the intracellular Ca²⁺ on responses to GABA was mimicked by activating excitatory receptors with 100 μM N-methyl-D-aspartate (NMDA). These findings suggest that modulation of GABA_A receptor activity by glutamate may be brought about via changes in intracellular Ca²⁺. Received: 20 May 1997 / Received after revision: 12 August 1997 / Accepted: 1 September 1997     

Stimulation of α1-adrenoceptors reduces glutamatergic synaptic input from primary afferents through GABAA receptors and T-type Ca channels

Activation of the descending noradrenergic system inhibits nociceptive transmission in the spinal cord. Although both α₁- and α₂-adrenoceptors in the spinal cord are involved in the modulation of nociceptive transmission, it is not clear how α₁-adrenoceptors regulate excitatory and inhibitory synaptic transmission at the spinal level. In this study, inhibitory and excitatory postsynaptic currents (IPSCs and EPSCs, respectively) were recorded from lamina II neurons in rat spinal cord slices. The specific α₁-adrenoceptor agonist phenylephrine significantly increased the frequency of GABAergic spontaneous IPSCs in a concentration dependent manner, and this effect was abolished by the α₁-adrenoceptor antagonist 2-(2,6-dimethoxyphenoxy)ethylaminomethyl-1,4-benzodioxane (WB4101). Phenylephrine also significantly reduced the amplitude of monosynaptic and polysynaptic EPSCs evoked from primary afferents. The inhibitory effect of phenylephrine on evoked monosynaptic glutamatergic EPSCs was largely blocked by the GABA_A receptor antagonist picrotoxin and, to a lesser extent, by the GABA_B receptor antagonist CGP55845. Furthermore, blocking T-type Ca²⁺ channels with amiloride or mibefradil diminished the inhibitory effect produced by phenylephrine or the GABA_A receptor agonist muscimol on monosynaptic EPSCs evoked from primary afferents. Collectively, these findings suggest that activation of α₁-adrenoceptors in the spinal cord increases synaptic GABA release, which attenuates glutamatergic input from primary afferents mainly through GABA_A receptors and T-type Ca²⁺ channels. This mechanism of presynaptic inhibition in the spinal cord may be involved in the regulation of nociception by the descending noradrenergic system.     

Phosphinic acid derivatives as baclofen agonists and antagonists in the mammalian spinal cord: an in vivo study

The actions of a series of derivatives of 3-aminopropyl-phosphinic acid as baclofen agonists and antagonists have been examined on the synaptic excitation of neurones by impulses in primary afferent fibres in the lumbar spinal cords of pentobarbitone-anaesthetised cats and rats. Both the pre-and postsynaptic inhibitory actions of microelectrophoretic (-)-baclofen were reduced by similarly administered CGP 35 348, 36 742, 46 381, 52 432, 54 626 and 55 845, the latter being the most potent antagonist. None of these antagonists either decreased or increased the excitability of spinal neurones, and the inhibitory action of GABA was reduced only by local concentrations of antagonists which also reduced the action of piperidine-4-sulphonic acid, a GABA_A agonist. Although the weak inhibitory effect of 3-aminopropylphosphinic acid in both the rat and the cat was not reduced by these baclofen antagonists, the pre-and postsynaptic inhibitory effects of 3-aminopropyl-methyl-osphinic acid (CGP 35 024), which was more potent than (-)-baclofen, were reduced by the antagonists. Like (-)-baclofen, CGP 35 024 was relatively ineffective in reducing transmitter release in the cord from the terminals of excitatory spinal interneurones, the terminals of excitatory tracts in the dorsolateral funiculus and the cholinergic terminals of motor axon collaterals. In both rat and cat cords, receptors for (-)-baclofen could not be demonstrated to be activated by microelectrophoretic GABA, possibly because of the predominantly dendritic location of GABA_B receptors. Spinal pre-and postsynaptic baclofen receptors appeared to be pharmacologically similar but differed from those in the higher central nervous system of the rat, where 3-aminopropylphosphinic acid has been reported to be an effective baclofen agonist. The compounds tested, particularly CGP 55 845 and 46 381, will be of use in further investigations of the physiological relevance of baclofen receptors at central synapses where GABA may be the transmitter.     

Contribution of GABA receptors to extinction of memory traces in normal conditions and in a depression-like state

A relationship between the effects of activation and blockade of GABA receptors on extinction of a conditioned passive avoidance reaction on the one hand and the type of receptor and initial psychoemotional state on the other was found in mice. Activation of GABA_A receptors with muscimol impaired extinction in normal conditions but had no effect on the delay in this process in mice with “behavioral despair” reactions. Activation of GABA_B receptors with baclofen accelerated extinction of the memory of fear in mice with the depression-like state. Blockade of GABA_A receptors with bicuculline had no extinction-modifying effect. Blockade of GABA_B receptors with faclofen promoted retention of the expression of fear in intact mice and acceleration of extinction in “depressed” mice. __________ Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 93, No. 11, pp. 1285–1291, November, 2007.     

The GABA<Subscript>A</Subscript> receptor-mediated recurrent inhibition in ventral compared with dorsal CA1 hippocampal region is weaker,decays faster and lasts less

Hippocampal functions appear to be segregated along the dorso-ventral axis of the structure. Differences at the cellular and local neuronal network level may be involved in this functional segregation. In this study the characteristics of CA1 recurrent inhibition (RI) were measured and compared between dorsal (DH, n = 95) and ventral (VH, n = 60) hippocampal slices, using recordings of suprathreshold field potentials. RI strength was estimated as the percentile decrease of the population spike (PS) amplitude evoked with an orthodromic stimulus (at the Schaffer collaterals) when preceded by an antidromic stimulus (at the alveus). Varying the interpulse interval (IPI) between the two stimuli, we estimated RI duration. Alvear stimulation produced significant PS suppression in both VH and DH at every IPI tested, from 10 to 270 ms. Moreover, gradually more oblique DH (but not VH) slices displayed increasing RI, which at IPIs ≤125 ms was reversibly abolished by the GABA_A receptor antagonist picrotoxin (10 μM). The GABA_A-mediated RI, measured under the blockade of GABA_B receptors, was weaker, decayed faster and lasted less in VH compared to DH slices, regardless of the slice orientation. Specifically, in VH compared to DH, the PS suppression at 20 ms was 34.4 ± 4.5% versus 69.9 ± 6.5% (P < 0.001), the time constant of RI decay was 29 ± 2.4 versus 87.5 ± 13.6 ms (P < 0.01) and the duration was 50 versus 125 ms (P < 0.001). Thus, GABA_A-mediated RI may control the CA1 excitatory output less effectively in VH compared to DH. The observed dorso-ventral differences in RI contribute to the longitudinal diversification of the structure and may underlie to some extent the region-specificity of hippocampal functions. Theodoros Petrides and Panagiotis Georgopoulos have equally contributed to the study.     

Contributions of Glycine and GABAA Receptors to the Generation of Inhibitory Postsynaptic Potentials in Frog Spinal Cord Motoneurons

Intracellular recording from lumbar motoneurons in isolated spinal cord preparations from the frog Rana ridibunda was used to study the contributions of glycine and GABA_A receptors to the generation of inhibitory postsynaptic potentials (IPSP) induced by microstimulation of fibers close to these motoneurons. IPSP were identified by blockade of excitatory synaptic transmission using kynurenate, CNQX, and AP-5 and by reversion of polarity on injection of a depolarizing current (1–10 nA) via the microelectrode. The selective glycine receptor antagonist strychnine at 1–5 μM decreased IPSP amplitude in all the motoneurons studied (by an average factor of 4.7), while the GABA_A receptor antagonist bicuculline at 50–70 mM decreased the amplitude (by an average factor of 1.6) in only some motoneurons, while no decrease occurred in others. Sequential application of strychnine and bicuculline completely blocked IPSP. These data support the view that postsynaptic inhibition in frog motoneurons is mediated mainly by glycine and to a lesser extent by GABA_A receptors. These latter are probably partially extrasynaptic.     

Axonal GABA receptors are selectively present on normal and regenerated sensory fibers in rat peripheral nerve

Summary A sucrose gap chamber was used to study the effect of gamma-aminobutyric acid (GABA) on normal and regenerating rat peripheral nerve fibers. Sciatic nerves and dorsal roots were depolarized by GABA and the GABA_A receptor subtype agonist muscimol, but not by the GABA_B receptor subtype agonist baclofen. Ventral root fibers were not affected by these agents, suggesting a selective presence of axonal GABA receptors on sensory fibers of mammalian peripheral nerves. Regenerating dorsal and ventral root fibers were studied 13 to 20 days following nerve crush. The regenerated dorsal root fibers were depolarized by GABA or muscimol, but the regenerated ventral root fibers were not. These results indicate that GABA receptors are selectively present on normal mammalian sensory axons, and are reestablished on regenerated sensory axons.     

Involvement of GABAB Receptors in Presynaptic Inhibition of Fibers of the Descending Projections of the Spinal Cord in the Frog Rana Ridibunda

Isolated spinal cord preparations from Rana Ridibunda frogs were used for studies of the effects of the GABA_B receptor agonists (–)-baclofen (50 and 100 M) and GABA (4–8 mM) and the specific GABA_B receptor antagonist 2-hydroxysaclofen (100 M) on the transmission of signals from fibers of the ventral columns monosynaptically connected with motoneurons in segments 9 and 10. These experiments showed that (–)-baclofen (50 and 100 M) produced significant and dose-dependent suppression of excitatory postsynaptic potentials (EPSP) in motoneurons and ventral root potentials evoked by stimulation of fibers of the ipsi- and contralateral ventral columns. The inhibitory effect of (–)-baclofen (100 M) on descending EPSP was 35–50% blocked by the GABA_B receptor antagonist 2-hydroxysaclofen (0.2 mM). The inhibitory effect of GABA (4–8 mM) on descending EPSP was 60% blocked by the GABA_A receptor antagonist picrotoxin (0.05 mM). (–)-Baclofen (50 M) and GABA (4 and 6 mM) were found to have inhibitory effects on ventral root potentials evoked by stimulation of the ipsi- and contralateral ventral columns. The data obtained here, as well as data obtained by pharmacological analysis and conditioning by stimulation of the ipsi- and contralateral ventral columns, are regarded as a significant argument supporting the existence of GABA_B receptor-mediated presynaptic inhibition of descending fibers connected monosynaptically to spinal cord motoneurons in the frog Rana Ridibunda.     

Nucleus of solitary tract mediates cardiac sympathetic afferent reflex in rats

This study is to determine whether the nucleus of solitary tract (NTS) is an important component of the central neurocircuitry of the cardiac sympathetic afferent reflex (CSAR) and whether the γ-aminobutyric acid (GABA) in the NTS modulates the CSAR. Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in sinoaortic-denervated and cervical-vagotomized anesthetized rats. The CSAR was evaluated by the RSNA response to epicardial application of capsaicin. The NTS microinjection of lidocaine or NTS electrolytic lesion inhibited the CSAR without significant effect on the RSNA and MAP. Selective lesion of the neuronal perikarya in NTS with kainic acid inhibited the CSAR and induced rapid decreases in RSNA and MAP followed by a slight increase in MAP. The NTS microinjection of GABA_A receptor agonist isoguvacine or GABA_B receptor agonist baclofen enhanced the CSAR, and increased the RSNA and MAP. GABA_A receptor antagonist gabazine or GABA_B receptor antagonist CGP-35348 attenuated the CSAR, and decreased the RSNA and MAP. The effects of isoguvacine and baclofen were abolished by the pretreatment with gabazine and CGP-35348, respectively. Nine days after iontophoretic injection of biotin-dextran (a retrograde tracer) into the dorsal horn of upper thoracic spinal cord, biotin-dextran-labeled terminations were found in the vicinity of glutamic acid decarboxylase (a marker for GABA neurons) staining neurons. The results indicate that the NTS is an important component of the central neurocircuitry of the CSAR. Both GABA_A and GABA_B receptors in NTS modulate the CSAR and these receptors play a tonic role in enhancing the CSAR.     

Lanthanum Potentiates GABA-Activated Currents in Rat Pyramidal Neurons of CA1 Hippocampal Field

In CA1 hippocampal pyramidal neurons, lanthanum ions increased the amplitude of GABA-activated currents and shifted the dose-dependence curve to the left, which attests to increased affinity of GABA_A-receptors to GABA. The data made it possible to compare the sensitivity GABA_A-receptors of pyramidal neurons and similar receptors of other cells to GABA and lanthanum. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 140, No. 10, pp. 398–401, October, 2005     

Differences in the Activation of Inhibitory Motoneuron Receptors in the Frog <Emphasis Type="Italic">Rana Ridibunda</Emphasis> by GABA and Glycine and Their Interaction

Intracellular recording of potentials was used in isolated spinal cord segments from the frog Rana ridibunda to compare the inhibitory effects of GABA and glycine on the motoneuron membrane. At equal concentrations, the response (a change in membrane potential) to application of glycine was 1.5–2 times greater than the response to GABA in terms of amplitude, and EC₅₀ values were 0.75 and 1.57 mM, respectively. The response to simultaneous application of GABA and glycine averaged 79.1 ± 2.4% (n = 19) of the sum of the individual responses and 130.1 ± 1.5% (n = 19) of the glycine response (partial occlusion). Preliminary application of glycine decreased the GABA response by 85.3 ± 0.2% (n = 10), while preapplication of GABA decreased the glycine response by only 52.9 ± 0.3% (n = 11). The glycine and GABA responses were specifically suppressed by strychnine and bicuculline. These results provide evidence that as in mammals, amphibian motoneurons have both glycine (predominantly) and GABA_A receptors; they also show that asymmetrical cross inhibition can occur.     

Effects of GABA and related agents on the electrical activity of hypothalamic ventromedial nucleus neurons in vitro

Summary Functional and neurochemical evidence suggests significant GABA participation in the basomedial hypothalamus. We have investigated electrophysiological effects of GABA using in vitro recording from hypothalamic tissue slices. Exogenous GABA inhibited 94 out of 121 ventromedial hypothalamic (VMN) neurons tested. In sixty-one percent of these GABA-responsive neurons, the inhibitory action of GABA was blocked by GABA_A antagonists, bicuculline methiodide (BMI) and picrotoxin (PTX). Nevertheless, many (27/69) GABA-responsive neurons were not sensitive to GABA_A blockers: BMI and PTX failed to antagonize inhibitory action of GABA. Most, if it not all, of these inhibitions can be accounted for by GABA_B effects, since baclofen powerfully inhibited 42 of 44 neurons tested. In addition to blocking the inhibitory action of exogenous GABA, BMI (55%) and PTX (36%) also caused changes of neuronal activity indicating blockade of intrinsic GABA-ergic action. Altogether, our results showed that, in the VMN, GABA acts through not only GABA_A but also GABA_B receptors to inhibit neuronal activity, and that there is tonic inhibition by intrinsic GABA neurons. These GABA actions may participate in behaviorallyrelevant VMN hypothalamic mechanisms.     

Mechanisms of kindling induced by norbornan intoxication

Single injection of norbornan induced kindling by disordering postsynaptic GABAergic structures. Modulation of GABA_A receptor chlorine ionic channels is most crucial, while disturbances in postsynaptic low-affinity GABA_A receptors are less important for this phenomenon. It is unlikely that GABA_B, dopamine, and muscarinic neurotransmitter structures are involved into this process. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 6, pp. 653–656, June, 1998