The neurophysiology of larval firefly luminescence: Direct activation through four bifurcating (DUM) neurons

Summary The paired lanterns of the larval fireflyPhoturis versicolor are bilaterally innervated by four dorsal unpaired median (DUM) neurons the somata of which are found in the terminal abdominal ganglion (A8) and which stain with Neutral Red (Fig. 1A). Both intra- and extracellularly recorded activity in these neurons is always associated with a bilateral glow response, or BGR (Figs. 3 and 4). Luminescence cannot be initiated or maintained in the absence of DUM neuron excitation. Furthermore, there is a linear causative relationship between the frequency of DUM neuron activity and the amplitude of the resultant BGR (Figs. 6 and 7).Due to the intrinsic bilateral morphology, firefly DUM neurons may be antidromically activated through either lantern nerve, resulting in the initiation of luminescence in the contralateral lantern (Figs. 8 and 9). This activation is unaffected by high Mg⁺⁺ saline indicating that the DUM neurons provide a direct pathway for conduction through the ganglion (Fig. 9). The DUM neurons receive synaptic input from axons descending through both anterior connectives, however, stimulation of only one connective results in a BGR since excitation is carried to both sides of the periphery through the bilateral axons.Firefly DUM neurons exhibit physiological qualities typical of neurosecretory cells: spikes are characterized by a slow time course and a long and deep afterhyperpolarization (Fig. 10). This is consistent with the observation that spontaneous firing rates are usually below 3 Hz, but nevertheless elicit a strong BGR (Figs. 3 and 5). The physiological evidence presented in this study correlates well with the morphological, pharmacological and biochemical evidence compiled from previous studies, which indicates that the four DUM neurons represent the sole photomotor output from the central nervous system to the larval lanterns. Evidence is discussed which indicates that these effects are mediated throught the release of octopamine, long presumed to be the lantern neurotransmitter. These results, therefore, describe a novel and unexpected role for DUM neurons in regulating an unusual invertebrate effector tissue and further expands the growing list of functions for octopamine in neural control mechanisms.Abbreviations A1-A7 first through seventh abdominal ganglia - A8 terminal abdominal ganglion - DUM dorsal unpaired median - BGR bilateral glow response     

In vitro antifungal, anti-elastase and anti-keratinase activity of essential oils of Cinnamomum-, Syzygium- and Cymbopogon-species against Aspergillus fumigatus and Trichophyton rubrum

This study was aimed to evaluate effects of certain essential oils namely Cinnamomum verum, Syzygium aromaticum, Cymbopogon citratus, Cymbopogon martini and their major components cinnamaldehyde, eugenol, citral and geraniol respectively, on growth, hyphal ultrastructure and virulence factors of Aspergillus fumigatus and Trichophyton rubrum. The antifungal activity of essential oils and their major constituents was in the order of cinnamaldehyde>eugenol>geraniol=C. verum>citral>S. aromaticum>C. citratus>C. martini, both in liquid and solid media against T. rubrum and A. fumigatus. Based on promising antifungal activity of eugenol and cinnamaldehyde, these oils were further tested for their inhibitory activity against ungerminated and germinated conidia in test fungi. Cinnamaldehyde was found to be more active than eugenol. To assess the possible mode of action of cinnamaldehyde, electron microscopic studies were conducted. The observations revealed multiple sites of action of cinnamaldehyde mainly on cell membranes and endomembranous structures of the fungal cell. Further, test oils were also tested for their anti-virulence activity. More than 70% reduction in elastase activity was recorded in A. fumigatus by the oils of C. verum, C. martini, eugenol, cinnamaldehyde and geraniol. Similar reduction in keratinase activity in A. niger was recorded for the oils of C. martini and geraniol. Maximum reduction (96.56%) in elastase activity was produced by cinnamaldehyde whereas; geraniol caused maximum inhibition (97.31%) of keratinase activity. Our findings highlight anti-elastase and anti-keratinase activity of above mentioned essential oils as a novel property to be exploited in controlling invasive and superficial mycoses.     

Molecular and pharmacological analysis of an octopamine receptor from American cockroach and fruit fly in response to plant essential oils

Octopamine receptors from American cockroach, Periplaneta americana (Pa oa1), and fruit fly, Drosophila melanogaster (OAMB), were cloned and permanently expressed in HEK-293 cells, and found to activate adenylate cyclase activity and increase [Ca2+]i levels through G-protein coupled receptor signaling pathways. Sequencing information (GenBank accession number AY333178) and functional data of Pa oa1 were recently published. Saturation binding analysis with 3H-yohimbine was performed with Pa oa(1) and OAMB expressed in COS-7 cells. The K(d) values were determined to be 28.4 and 43.0 nM, respectively. B(max) was determined to be 11.8 and 8.04 pmol receptor/mg protein, respectively. Competitive binding data using cell membranes expressing either OAMB or Pa oa1 demonstrated significantly decreased binding activity in binding assays performed in the presence of plant essential oils, eugenol, cinnamic alcohol, and trans-anethole. Eugenol decreased cAMP level in HEK-293 cells expressing Pa oa1, but trans-anethole increased cAMP in HEK-293 cells expressing OAMB. All three chemicals increased [Ca2+]i level in both cell models. Toxicity data against fruit flies and American cockroaches demonstrated species differences in response to treatment with tested plant essential oils. The toxicity of tested chemicals against wild type and octopamine mutant (iav) fly strains suggested that an octopamine receptor mediates the toxicity of cinnamic alcohol, eugenol, trans-antehole, and 2-phenethyl propionate against fruit flies. Collectively, the data suggest a correlation between cellular changes induced by tested plant essential oils and their toxicity against fruit fly and American cockroach.     

Antifungal action and antiaflatoxigenic properties of some essential oil constituents

The effect of 20 essential oil constituents on Aspergillus flavus growth and aflatoxin production was tested at the level of 1000 ppm. Some of the tested oils exhibited inhibitory effects on fungal growth and toxin formation. Five oils, namely geraniol, nerol and citronellol (aliphatic oils), cinnamaldehyde (aromatic aldehyde) and thymol (phenolic ketone), completely suppressed growth and aflatoxin synthesis. Trials for determining the minimum inhibitory concentration (MIC) of these oils revealed that geraniol, nerol and citronellol were effective at 500 ppm, while thymol and cinnamaldehyde were highly effective at doses as low as 250 and 200 ppm, respectively. It was observed that citral, citronellal and eugenol prevented fungal growth and toxin formation for up to 8 d. However, after 15 d of incubation, toxin production was greater than the controls.     

Interaction of formamidines with octopamine-sensitive adenylate cyclase receptor in the nerve cord of Periplaneta americana L

Chlordimeform (CDM) and demethylchloridimeform (DCDM) mimic the action of octopamine in elevating adenylate cyclase activity in intact nerve cords of the American cockroach, Periplaneta americana. At a concentration of 1 x 10(-5)M, DCDM (13.5x increase within 20 minutes) is a more potent effector of the response than CDM (3x increase within 20 minutes), but both compounds show less efficacy than octopamine (23.5x increase within 15 minutes). DCDM also mimics the stimulatory effect of octopamine on adenylate cyclase activity in nerve cord homogenates whereas CDM has no demonstrable effect on this preparation. The octopamine- and DCDM-induced responses are competitively inhibited by phentolamine (1 x 10(-6)M) and cyproheptadine (1 x 10(-6)M) but not by propranolol (1 x 10(-6)M). DCDM and CDM inhibit the octopamine-induced activation of adenylate cyclase by 33% and 44% respectively. The results are discussed in light of the proposal that DCDM serves as a partial agonist and CDM as an antagonist of the octopamine receptor.     

Central nervous sensitization and dishabituation of reflex action in an insect by the neuromodulator octopamine

Habituation of excitatory synaptic inputs onto identified motor neurons of the locust metathoracic ganglion, driven electrically and by natural stimuli, was examined using intracellular recording. Rapid progressive reduction in amplitude of EPSPs from a variety of inputs onto fast-type motor neurons occurred. The habituated EPSPs were quickly dishabituated by iontophoretic release of octopamine from a microelectrode into the neuropilar region of presumed synaptic action. The zone within which release was effective for a given neuron was narrowly-defined. With larger amounts of octopamine applied at a sensitive site the EPSP became larger than normal, and in many instances action potentials were initiated by the sensitized response. Very small EPSPs onto a motor neuron, which were associated with proprioceptive feedback, and which were originally too small to be detected above the noise, were potentiated to a level of several mV by the iontophoresed octopamine. A DUM neuron (presumed to be octopaminergic) was found, whose direct stimulation was followed by a strong dishabituating and sensitizing action leading to spikes, of inputs to an identified flexor tibiae motor neuron. The action and its time course were closely similar to those evoked by octopamine iontophoresed into the neuropil in the region of synaptic inputs to the motor neuron. It is concluded that DUM (octopaminergic) neurons exert large potentiating actions on central neuronal excitatory synaptic transmission in locusts.     

Tyramine as a possible neurotransmitter/neuromodulator at the spermatheca of the African migratory locust, Locusta migratoria

Tyramine-like immunoreactivity was identified in neurons of the VIIIth abdominal ganglion and in axons projecting to the spermatheca of adult females of Locusta migratoria. Tyramine-like immunoreactive processes were also found throughout all regions of the spermatheca and tyramine-like immunoreactive bipolar or multipolar neurons were present on the spermathecal sac. HPLC coupled with electrochemical detection revealed more tyramine than octopamine present in spermathecal tissue. Electrical stimulation of the ventral ovipositor nerve resulted in a significant increase in calcium-dependent release of tyramine from the spermatheca. Both tyramine and octopamine increase the frequency and basal tonus of spermathecal contractions in a dose-dependent manner, with octopamine having a lower threshold. When tyramine is applied along with a half maximal octopamine dose, there is an additive effect on contractions of the spermatheca with slight synergistic effects at lower doses of tyramine. High concentrations of tyramine (10(-4)M) stimulated increases in cyclic AMP levels of the spermatheca; an effect blocked by phentolamine. Phentolamine has a higher affinity (and thus a lower IC(50) value congruent with5.6x10(-8)M) than yohimbine (IC(50) congruent with1.1x10(-4)M) in reducing tyramine-induced spermathecal contractions. Taken together, these results suggest that tyramine may be a co-transmitter with octopamine at the spermatheca, with both neuroactive chemicals acting on an octopamine receptor.     

Genetic diversity of Ocimum gratissimum L. based on volatile oil constituents, flavonoids and RAPD markers

Morphological, chemical and genetic differences of 12 tree basil (Ocimum gratissimum L.) accessions were studied to determine whether volatile oils and flavonoids can be used as taxonomical markers and to examine the relationship between RAPDs to these chemical markers. Eugenol, thymol, and geraniol were the major volatile oil constituents found in Ocimum gratissimum. Xantomicrol and cirsimaritin were the major external flavones. The accessions morphologically described as O. gratissimum var. gratissimum contained eugenol as the major volatile oil constituent, and cirsimaritin as the major flavone. Ocimum gratissimum var. macrophyllum accessions contained thymol as the major volatile oil constituent, and xantomicrol as the major flavone. A distinct essential oil and flavone chemotype (producing geraniol and a mixture of the flavones cirsimaritin, isothymusin, xanthomicrol, and luteolin) was found in an accession genetically more distant from the other two groups when analyzed by molecular markers. The accessions could be divided based on volatile oil constituents into six groups: (1) thymol: alpha-copaene (ot24, ot25, ot26, and ot28); (2) eugenol:spathulenol (ot17, ot63, and ot52); (3) thymol:p-cymene (ot65); (4) eugenol:gamma-muurolene (ot27 and ot29); (5) eugenol:thymol: spathulenol (ot85); and (6) geraniol (ot84). Cluster analysis of RAPD markers showed that there are three groups that are distinct genetically and highly correlated (r=0.814) to volatile oil constituents.     

几种驱避化合物对白纹伊蚊寄主搜寻能力的影响

研究了白纹伊蚊Aedes albopictus在含不同浓度的驱避化合物的空间内停留不同时间后,对其寄主搜寻能力的影响。结果显示：在密闭空间中, 分别以0.013～0.500 μg/cm³浓度的柠檬醛、丁香酚、芳樟醇、香叶醇、茴香醛处理白纹伊蚊24～96 h后,试蚊均出现不同程度的定向寄主抑制,其中以茴香醛及香叶醇抑制效果最佳,但香茅醛各处理组试蚊均未受到影响。白纹伊蚊搜寻定向寄主能力受到抑制的个体,在实验室正常饲养后,可逐渐恢复;但茴香醛0.250 μg/cm³处理试虫96 h后,一直未能恢复正常的吸血行为。研究结果提示,茴香醛与香叶醇作为优良的空间驱避剂,在白纹伊蚊防控技术领域可发挥重要作用。     

Activity of essential oils and individual components against acetyl- and butyrylcholinesterase

We have tested acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of nineteen essential oils obtained from cultivated plants, namely one from Anethum graveolens L. (organic fertilizer), two from Foeniculum vulgare Mill. collected at fully-mature and flowering stages (organic fertilizer), two from Melissa officinalis L. (cultivated using organic and chemical fertilizers), two from Mentha piperita L. and M. spicata L. (organic fertilizer), two from Lavandula officinalis Chaix ex Villars (cultivated using organic and chemical fertilizers), two from Ocimum basilicum L. (green and purple-leaf varieties cultivated using only organic fertilizer), four from Origanum onites L., O. vulgare L., O. munitiflorum Hausskn., and O. majorana L. (cultivated using organic fertilizer), two from Salvia sclarea L. (organic and chemical fertilizers), one from S. officinalis L. (organic fertilizer), and one from Satureja cuneifolia Ten. (organic fertilizer) by a spectrophotometric method of Ellman using ELISA microplate-reader at 1 mg/ml concentration. In addition, a number of single components widely encountered in most of the essential oils [gamma-terpinene, 4-allyl anisole, (-)-carvone, dihydrocarvone, (-)-phencone, cuminyl alcohol, cumol, 4-isopropyl benzaldehyde, trans-anethole, camphene, iso-borneol, (-)-borneol, L-bornyl acetate, 2-decanol, 2-heptanol, methyl-heptanol, farnesol, nerol, iso-pulegol, 1,8-cineole, citral, citronellal, citronellol, geraniol, linalool, alpha-pinene, beta-pinene, piperitone, iso-menthone, menthofurane, linalyl oxide, linalyl ester, geranyl ester, carvacrol, thymol, menthol, vanilline, and eugenol] was also screened for the same activity in the same manner. Almost all of the essential oils showed a very high inhibitory activity (over 80%) against both enzymes, whereas the single components were not as active as the essential oils.     

Inhibitory actions of eugenol on rat isolated ileum

The effects of eugenol (1-2000 microM) on rat isolated ileum were studied. Eugenol relaxed the basal tonus (IC50 83 microM) and the ileum precontracted with 60 mM KCl (IC50 162 microM), an action unaltered by 0.5 microM tetrodotoxin, 0.2 mM N(G)-nitro-L-arginine methyl ester, 0.5 mM hexamethonium, and 1 microM indomethacin. Eugenol did not alter the resting transmembrane potential (Em) of the longitudinal muscle layer under normal conditions (5.0 mM K+) or in depolarised tissues. Eugenol reversibly inhibited contractions induced by submaximal concentrations of acetylcholine (ACh) and K+ (40 mM) with IC50 values of approximately 228 and 237 microM, respectively. Eugenol blocked the component of ACh-induced contraction obtained in Ca(2+)-free solution (0.2 mM EGTA) or in the presence of nifedipine (1 microM). Our results suggest that eugenol induces relaxation of rat ileum by a direct action on smooth muscle via a mechanism largely independent of alterations of Em and extracellular Ca2+ influx.     

Eugenol depresses synaptic transmission but does not prevent the induction of long-term potentiation in the CA1 region of rat hippocampal slices

Using field potential recording in the CA1 region of the rat hippocampal slices, the effects of eugenol on synaptic transmission and long-term potentiation (LTP) were investigated. Population spikes (PS) were recorded in the stratum pyramidal following stimulation of stratum fibers. To induce LTP, eight episodes of theta pattern primed-bursts (PBs) were delivered. Eugenol decreased the amplitude of PS in a concentration-dependent manner. The effect was fast and completely reversible. Eugenol had no effect on PBs-induced LTP of PS. It is concluded that while eugenol depresses synaptic transmission it does not affect the ability of CA1 synapses for tetanus-induced LTP and plasticity.     

Effect of somatostatin on neurons of the partially deafferented rabbit amygdala

Changes in spontaneous activity of 291 neurons in the rabbit amygdala were analyzed during microelectrophoretic application of somatostatin under pentobarbital anesthesia. Somatostatin was found both to enhance and to inhibit the spontaneous activity of these cells, by contrast with the exclusively inhibitory effect on spontaneous activity of hypothalamic neurons described previously. After partial chronic deafferentiation of the amygdala, 76% of 103 neurons responded to somatostatin application; 90% of the responding cells, in which the initial spontaneous firing rate was 6–20 spikes/sec, responded by more rapid firing, and only 10% of neurons (with an initial spontaneous discharge frequency of over 20 spikes/sec) showed a decrease in firing rate. Neuronal responses in the amygdala to somatostatin, glutamate, and noradrenalin are compared. Preliminary application of noradrenalin caused an increase in the number of inhibitory responses on subsequent application of somatostatin to the same cell.M. V. Lomonosov Moscow State University. Translated from Neirofiziologiya, Vol. 14, No. 6, pp. 601–607, November–December, 1982.     

Interaction between octopamine and proctolin on the oviducts of Locusta migratoria

The biogenic amine octopamine and the pentapeptide proctolin are two important neuroactive chemicals that control contraction of the oviducts of the African locust Locusta migratoria. The physiological responses and signal transduction pathways used by octopamine and proctolin have been well characterized in the locust oviducts and this therefore provides the opportunity to examine the interaction between these two pathways. Octopamine, via the intracellular messenger adenosine 3',5'-cyclic monophosphate (cyclic AMP), inhibits contraction of the oviducts, while proctolin, via the phosphoinositol pathway, stimulates contraction. We have examined the physiological response of the oviducts to combinations of octopamine and proctolin and also looked at how combinations of these affect one of the main intracellular mediators of the octopamine response, namely cyclic AMP. It was found that application of octopamine to the oviducts led to a dose-dependent reduction in tonus of the muscle and also a decrease in the amplitude and frequency of spontaneous phasic contractions. Octopamine-induced relaxation was enhanced in the presence of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX). Octopamine was also able to inhibit proctolin-induced contractions of the oviducts in a dose-dependent manner. A 10(-9) M proctolin-induced contraction was inhibited by 83% in the presence of 10(-5) M octopamine, and was completely inhibited in the presence of 10(-5) M octopamine plus 5x10(-4) M IBMX. Octopamine led to a dose-dependent increase in cyclic AMP content as measured by radioimmunoassay. In the presence of 10(-9) M proctolin, this octopamine-induced increase in cyclic AMP was reduced by as much as 60%. Proctolin also caused a dose-dependent decrease in the cyclic AMP elevation produced by 5x10(-6) M octopamine. These results indicate that octopamine and proctolin can antagonize each other's physiological response when added in combination, and that proctolin is able to modulate the response of the oviducts to octopamine by influencing cyclic AMP levels.     

Inhibition of Ascosphaera apis by citral and geraniol

In vitro tests showed that citral and geraniol inhibited the fungus Ascosphaera apis which causes chalkbrood disease in the honeybee, Apis mellifera. The vapors of 5 μl of citral or 10 μl of geraniol per culture dish prevented vegetative growth. Daily applications of 30 μl of citral per dish killed sporulated cultures within 48 hr. However, A. apis spores in dried larval remains (mummies) survived 96-hr exposure to the vapors of 30 μl of citral per dish per day.Vapors of a geranic and nerolic acid mixture, 2-heptanone, isopentyl acetate, octanoic acid, and citronella and melissa oils were less inhibitory than citral or geraniol. Potassium sorbate, sodium propionate, and tetracycline had no inhibitory effect when placed on the culture medium. Remains of larvae killed by American foulbrood disease caused only a slight reduction in the growth of A. apis.     

Release of octopamine by Leydig cells in the central nervous system of the leech Macrobdella decora, and its possible neurohormonal role

1. The release of octopamine by the central nervous system of the leech Macrobdella decora was examined. Isolated ganglia or chains of ganglia were incubated in salines of varying composition, and the release of octopamine into the perfusate was measured using a radioenzymatic method. In some experiments this release was correlated with the electrical activity of the octopamine-containing Leydig cells, as measured via a microelectrode in the cell body. 2. Chains of ganglia incubated in normal saline released 0.04 pmol octopamine/ganglion/3 min incubation period. This amount was not significantly increased by either the monoamine oxidase inhibitor iproniazid phosphate (0.1 mM) or the uptake inhibitor desipramine (10 microM) alone, but was by both together. Nominally calcium-free saline containing 20 mM Mg++ significantly decreased octopamine release. 3. High K+ saline increased octopamine release significantly in both standard saline and one containing the blocking agents. This increase was sevenfold in saline containing iproniazid phosphate and desipramine, and was significantly greater than that obtained in saline without the blockers. This provides further evidence for the role of octopamine as a neuroactive substance in the leech by indicating the existence of possible mechanisms for its uptake and/or inactivation. 4. Octopamine release was positively correlated with the firing frequency of Leydig cells. No release was detectable when the cells were prevented from firing by the injection of hyperpolarizing current. Release was frequency-dependent when the cells fired at frequencies of 0.1-1.0 spikes/s. Elevating the external calcium concentration from 1.8 to 5.4 mM significantly increased octopamine release at all frequencies tested, except for 0 spikes/s, at which release remained below detectabilty.(ABSTRACT TRUNCATED AT 250 WORDS)     

Activation of DUM cell interneurons by ventral giant interneurons in the cockroach, Periplaneta americana

Dorsal unpaired median (DUM) cells in orthopteran insects are known to contain the neuromodulatory substance octopamine, and DUM cells with peripheral axons augment synaptic activity at neuromuscular junctions. One of the most studied systems in the cockroach is the giant interneuron (GI) system which controls the initial movements of a wind-mediated escape response. Our data demonstrate that DUM cells that are restricted to the central nervous system (DUM interneurons) receive inputs from ventral giant interneurons (vGIs) but not from dorsal giant interneurons (dGIs). In contrast, DUM cells that have peripheral axons consistently fail to be excited by any giant interneurons. The DUM interneurons are excited by vGIs on both sides of the CNS and, when the vGIs are excited in pairs, summation occurs. Wind fields that have been generated for two of the DUM interneurons are omnidirectional. These data, taken along with the known association of DUM cells with the neuromodulatory substance octopamine, suggest that the DUM interneurons may act to modulate central synapses.     

The antennal motor system of crickets: modulation of muscle contractions by a common inhibitor,DUM neurons,and proctolin

In the crickets Gryllus bimaculatus and Gryllus campestris, the two intrinsic antennal muscles in the scape (first antennal segment) control antennal movements in the horizontal plane. Of the 17 excitatory antennal motoneurons, three motoneurons, two fast and one slow, can be stimulated selectively and their effect on muscle contraction, i.e. antennal movement, measured. Simultaneously, either a common inhibitor (CI) neuron or two DUM neurons can be stimulated and the effect on the slow and/or fast muscle contraction measured. The activity of the common inhibitor affected only slow muscle contractions. It decreased contraction rate, increased relaxation rate and suppressed prolonged muscle tension. This effect was blocked by picrotoxin. DUM neuron stimulation affected both slow and fast contractions. It reduced slow and enhanced fast contractions but in only 10% of the experiments could this effect be detected. DUM neuron activity could be mimicked by octopamine application. Proctolin application enhanced both slow and fast contractions but did not increase muscle tension in the absence of motoneuron activity. The results are discussed in relation to the large variability of possible antennal movements during behaviors.Abbreviations CI common inhibitor neuron - DUM dorsal unpaired median neuron     

Excitation by dopamine D-2 receptor agonists, bromocriptine and LY 171555, in caudate nucleus neurons activated by nigral stimulation

Electrophysiological studies using cats anesthetized with alpha-chloralose were carried out to determine whether or not the dopamine D-2 receptor mediates the excitation of the caudate nucleus (CN) neurons activated by stimulation of the substantia nigra (SN). Microiontophoretic application of domperidone (D-2 antagonist) produced a significant inhibition of spikes elicited by SN stimulation in 20 of 27 CN neurons. When bromocriptine and LY 171555 (D-2 agonists) were iontophoretically applied to the CN neurons in which the SN-induced spikes were inhibited by domperidone, an increase in spontaneous firing rate was observed in 18 of 20 neurons and all of 10 neurons tested, respectively. However, no alterations of firing occurred with bromocriptine or LY 171555 in any 7 neurons in which the SN-induced spikes were not affected by domperidone. The increase in firing rate by the D-2 agonists was apparently antagonized during simultaneous application of domperidone and haloperidol, but not affected during application of SCH 23390 (D-1 antagonist). These results strongly suggest that the spike generation of the CN neurons upon SN stimulation is mediated by the dopamine D-2 receptor.     

Inhibition by talipexole, a thiazolo-azepine derivative, of dopaminergic neurons in the ventral tegmental area.

A microiontophoretic study using rats anesthetized with chloral hydrate and immobilized with gallamine triethiodide was carried out to compare the effect of talipexole (B-HT 920 CL2:2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo [4,5-d]-azepine-dihydrochloride), a dopamine autoreceptor agonist, on dopaminergic neurons in the ventral tegmental area (VTA) to non-dopaminergic neurons in the VTA. VTA neurons were classified into two types according to the responses to antidromic stimulation of the nucleus accumbens (Acc): type I neurons with a long spike latency (8.69 +/- 0.24 msec) upon Acc stimulation and low spontaneous firing rate (6.80 +/- 1.34/sec), and type II neurons with a short latency (2.76 +/- 0.20 msec) and high spontaneous firing rate (26.77 +/- 7.05/sec), probably corresponding to dopaminergic and non-dopaminergic neurons, respectively. In type I neurons, microiontophoretic application of talipexole and dopamine inhibited antidromic spike generation elicited by Acc stimulation, and talipexole-induced inhibition was antagonized by domperidone (dopamine D-2 antagonist). In type II neurons, however, the antidromic spikes were not affected by either talipexole or dopamine. Furthermore, spontaneous firing was also inhibited by iontophoretically applied talipexole and dopamine in most type I neurons, but rarely affected by either drug. Inhibitory effects of talipexole were antagonized by domperidone. These results suggest that talipexole acts on dopamine D-2 receptors, thereby inhibiting the dopaminergic neurons in the VTA.