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1.
The action of cholecystokinin octapeptide (CCK-8) on rat neostriatal dopamine (DA) D 2 receptors was evaluated in membrane binding experiments. 0.1 nM of CCK-8 inreased the Kd value of the D 2 agonist [ 3H]N-propylnorapomorphine (NPA) binding sites by 42%. The CCK B antagonist PD134308 blocked this action. Kinetic analysis demostrated that this effect of CCK-8 was related to a reduction by 45% of the association rate constant of [ 3H]NPA. In contrast, 1 nM of CCK-8 decreased the KH and the KL values of DA for the D 2 antagonist [ 3H]raclopride binding sites by 56% and 50%, respectively. Both the CCK A antagonist L364718 and the CCK B antagonist PD134308 blocked this effect. The D 1 antagonist SCH23390 counteracted the CCK-8 induced decrease in the KH and the KL values of DA, and allowed 1 nM of CCK-8 to produce a significant increase in the IC 50 value of NPA for the [ 3H]raclopride binding sites. These results indicate that CCK-8 can reduce the affinity of the neostriatal D 2 agonist binding sites, but increase the affinity of D 2 receptors for DA. D 1 receptors may exert a switching role in the modulation of the neostriatal D 2 receptors by the CCK receptors. 相似文献
2.
Somatostatin (SS)-containing perikarya located within the hypothalamic periventricular nucleus (PeVN) comprise a heterogenous population of neurons with both local intrahypothalamic and distant extrahypothalamic axonal projection sites. The close proximity of SS perikarya and their dendrites to dopaminergic (DA) neuronal processes in the PeVN suggests that these peptidergic neurons may be regulated by DA receptor-mediated mechanisms. To test this, the effects of the D 1 agonist SKF 38393 and D 2/3 agonist quinelorane were examined on expression of the immediate early gene products Fos and its related antigens (FRA) in SS-immunoreactive (IR) neurons in the PeVN. SS-IR neurons were located in the most medial portion of the PeVN bordered medially by the third ventricle and laterally by tyrosine hydroxylase (TH)-IR neurons. In control rats, 10–15% of all SS-IR neurons contained FRA-IR. Activation of D 1 receptors with SKF 38393 had no effect on either the total number of SS-IR neurons or the number of SS-IR neurons containing FRA-IR. In contrast, activation of D 2/3 receptors with quinelorane decreased the number of SS-IR neurons containing FRA-IR, without affecting the total number of SS-IR neurons. The D 2/3 antagonist raclopride had no effect per se, but prevented the quinelorane-induced decrease in the number of SS neurons expressing FRA-IR. These results reveal that activation of D 2/3 (but not D 1) receptors inhibits expression of the immediate early gene products FRA in SS-containing neurons in the PeVN, but expression of FRA in SS neurons is not tonically inhibited by dopamine acting on D 2/3 receptors. 相似文献
3.
Previous research indicates that prenatal cocaine (pCOC)-exposure results in greater 5-HT 3 agonist-induced inhibition of electrically evoked [ 3H]acetylcholine (ACh) overflow in rat striatal slices. The present study examines the effects of fluoxetine (FLU)-induced and exogenous serotonin (5-HT) on electrically evoked ACh release from striatal slices prepared from adult male and female (in periods of diestrus or proestrus) rats exposed to saline or cocaine in utero. Additionally, we assessed the impact of monoaminergic receptor stimulation on evoked ACh release by superfusion with selective 5-HT 2, 5-HT 3 and D 2 receptor antagonists in the presence of FLU-induced and exogenous 5-HT and measuring the capacity of these drugs to reverse inhibitory effects of 5-HT. Given our previous findings of accentuated inhibition of ACh release by 5-HT 3 agonism in striata of pCOC-exposed adult rats, we hypothesized that superfusion of endogenous and exogenous 5-HT would lead to greater suppression of evoked ACh release in this group of animals. Our results indicated that ACh release from slices of all prenatal saline (pSAL) rats was inhibited comparably by FLU (10 μM)-elicited increases in endogenous 5-HT or by increases elicited with application of exogenous 5-HT (5 μM). Robust FLU-mediated inhibition of ACh release was evident in slices from pCOC male and pCOC diestrus female rats vs. their respective PSAL control groups. Superfusion of striatal slices with 5-HT (5 μM) produced a pattern of ACh inhibition similar to that produced by FLU; however, the magnitude of ACh inhibition was consistently greater than that observed with FLU. Inhibition of ACh overflow by FLU was blocked by co-superfusion with ketanserin, a 5-HT 2 receptor antagonist, ICS-205,930, a 5-HT 3 receptor antagonist or sulpiride, a D 2 receptor antagonist. Conversely, serotonergic inhibition of ACh overflow was only blocked by a high concentration of ICS-205,930 (5 μM) and was completely reversed by sulpiride (1 μM). Collectively, these findings demonstrate serotonergic modulation of cholinergic neurons varying as a function of prenatal treatment, sex and, for females, phase of estrous. Inhibition of ACh release by 5-HT appears to be mediated by a complex relationship between 5-HT 2, 5-HT 3 and D 2 receptor regulation, as the blockade of any of these receptors reversed the inhibitory effects of FLU on ACh release. Conversely, in the case of exogenous 5-HT-induced inhibition, only blockade of D 2 receptors and high concentrations of the 5-HT 3 receptor antagonists were capable of reversing monoaminergic inhibition. These data support the hypothesis that the enhanced serotonergic modulation of ACh neurons in pCOC-exposed animals is largely mediated by dopamine (DA) and reflect a major biochemical persistence of neurodevelopmental adaptations elicited by early cocaine exposure. 相似文献
5.
The serotonin agonist 8-hydroxy-di-propylaminotetralin (8-OH-DPAT), injected systemically or directly into the medial preoptic area (MPOA), reduces the ejaculatory threshold in male rats. While 8-OH-DPAT has been characterized as an agonist at the 5-HT 1A receptor, it also acts at other receptor sites including the dopamine D 2 receptor. The current experiments investigated whether 8-OH-DPAT injected into the MPOA facilitates male sexual behavior through stimulation of the 5-HT 1A receptor or the dopamine D 2 receptor. Experiment 1 co-administered 8-OH-DPAT (6 μg) with either the 5-HT 1A antagonist 4-iodo- N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]- N-2-pyridinyl-benzamide hydrochloride (MPPI) (10 μg) or the D 2 antagonist raclopride (10 μg). Raclopride blocked 8-OH-DPAT's facilitative effects on ejaculation frequency and latency, while the 5-HT 1A antagonist was ineffective. In Experiment 2, 8-OH-DPAT (500 μM), retrodialyzed into the MPOA through a microdialysis probe, enhanced male copulatory behavior similarly to the microinjection, increasing ejaculation frequency and decreasing ejaculation latency, postejaculatory interval and mount frequency. Retrodialyzing 8-OH-DPAT through a microdialysis probe in the MPOA had been previously shown to increase extracellular levels of dopamine and serotonin. The data from the present studies suggest that the effects of 8-OH-DPAT in the MPOA on male rat copulatory behavior may be mediated, at least in part, either directly through 8-OH-DPAT's activity at D 2 receptors or indirectly through 8-OH-DPAT's ability to increase extracellular dopamine. 相似文献
6.
The interactions between dopamine and carbachol on the excitatory synaptic transmission were studied in rat neostriatal slices using an intracellular recording method. Excitatory postsynaptic potentials (EPSPs) were evoked by cortical stimulation. Application of dopamine (DA; 0.1 μM) or carbachol (0.1 μM) produced a dramatic and reversible inhibition of the EPSP amplitude. The inhibitory effect induced by carbachol was markedly attenuated in the presence of either DA (0.1 μM) or the selective D 2 dopaminergic receptor agonist (±)-2-(N-phenylethyl-N-propyl) amino-5-hydroxytertralin (PPHT; 0.1 μM), but not by the D 1 dopaminergic receptor agonist (±)-7,8-dihydroxy-3-allyl-1-phenyl-2, 3, 4, 5-tetrahydro-1H-3-benzazepine (SKF-38393; 0.1 μM) or the D 3 dopaminergic receptor agonist R(−)-(4aS, 10bS)-3, 4, 4a, 10b-tetrahydro-4-propyl-2H, 5H-[1] benzogyrano-[4,3-b]-1, 4-oxazin-9-ol (PD-128,907; 0.1 μM). Conversely, muscarinic receptor activation with carbachol (0.1 μM) also completely abolished the DA-induced depression of the EPSP amplitude. In addition, the inhibitory effect of DA on the carbachol-induced depression of the EPSP amplitude was antagonized by sulpiride (1 μM), a selective D 2 dopaminergic receptor antagonist. However, D 1 dopaminergic receptor antagonist (±)-7-bromo-8-hydroxy-3-methyl-1-phenyl-2, 3, 4, 5-tetrahydro-3-benzazepine (SKF-83566; 1 μM) did not affect DA's inhibition. Rp-adenosine-3′,5′-cyclic monophosphothioate (Rp-cAMPS; 25 μM), a potent inhibitor of cAMP-dependent protein kinase A (PKA), alone decreased the amplitude of EPSP below baseline values and mimicked the inhibitory effect of DA on the carbachol-induced depression of the EPSP amplitude. Based on these findings, we conclude that the inhibitory effects of D 2 dopaminergic receptor and muscarinic receptor activation on the excitatory synaptic transmission in the neostriatum are non-additive and therefore are antagonistic interactions. Furthermore, the effect of muscarinic receptor stimulation will depend on the extent of D 2 dopaminergic receptor activation and the modulation of the cellular PKA-dependent messenger system seems to contribute to their interactions. © 1996 Wiley-Liss, Inc. 相似文献
7.
Bilateral intranigral administration of the selective NK-1 tachykinin receptor agonist [AcArg 6, Sar 9, Met(O 2) 11]SP 6–11 (0–11 nmol total bilateral dose) selectively induced grooming in rats. This response was blocked by concurrent intranigral administration of the NK-1 tachykinin receptor antagonist RP 67580 (2 nmol), but not by NK-2 (L-659, 877) or NK-3 ([Trp 7, β-Ala 8]NKA 4–10) antagonists. Pretreatment with systemic opioid (naloxone 1.5 mg/kg) and D 1 dopamine (SCH 23390 100 μg/kg) receptor antagonists also attenuated tachykinin-induced grooming, which was unaffected by D 2 dopamine (sulpiride 30 mg/kg) or 5-HT 2A+C (ritanserin 2 mg/kg) antagonists. Grooming induced by intranigral [AcArg 6, Sar 9, Met(O 2) 11]SP 6–11 was also attenuated by bilateral 6-hydroxydopamine lesions of te substantia nigra. These findings indicate that grooming induced by intranigral tachykinins reflects activation of NK-1 receptors and is dependent upon endogenous dopamine and consequent selective stimulation of D 1 dopamine receptors. 相似文献
8.
In rats, the non-opioid β-endorphin (βE) fragment desenkephalin-γ-endorphin (DEγE, βE 6–17) antagonizes the hypomotility induced by a small dose of dopamine (DA) receptor agonists. It has been suggested that DEγE might act in this respect by a direct or indirect blockade of presynaptically located DA receptors in the nucleus accumbens, thereby causing an increase of DA release. Therefore in the present study the effect of DEγE was examined on DA receptor agonist-induced inhibition of the electrically evoked release of previously accumulated [ 3H]DA from rat nucleus accumbens slices in vitro. The DA receptor agonists apomorphine, LY 171555 and n,n-di-n-propyl-7-hydroxy-2-aminotetralin (DP-7-AT) inhibited in a concentration-dependent manner the electrically evoked release of [ 3H]DA. The selective D 2 receptor antagonist (−)-sulpiride blocked the effects of apomorphine, corroborating that the DA receptor involved is of a D 2 type. DEγE was tested at several concentrations (10 −9–10 −6) and under various experimental conditions. DEγE, by itself, did not affect either the electrically stimulated or the basal release of [ 3H]DA. The inhibiting effect of DA receptor agonists was slightly reduced by DEγE, but this effect was present in some experiments only. It is concluded that DEγE does not function as an antagonist for the DA receptor mediating DA release and that the interaction observed in behavioural experiments between DA agonists and DEγE does not occur at the level of this receptor. 相似文献
9.
Extracellular single unit responses were recorded from 381 neurons in the neostriatum of urethane-anesthetized rats. Single pulse stimulation of the sensory motor cortex produced strong excitatory responses in neostriatal neurons with a mean onset latency of 7.9 ms. A train of 10 pulses (0.15 ms, 300-600 microA) at 10 Hz delivered to the substantia nigra 100 ms before cortical stimulation attenuated the original excitatory response of 22 of 53 striatal neurons tested and enhanced the excitatory response of 12 of these neurons. These attenuating and enhancing effects were reduced or abolished by the systemic administration of haloperidol, a dopamine antagonist. Single pulse nigral stimulation 100 ms before the cortical stimulation had little or no effect on the excitatory response of neostriatal neurons. The iontophoretic application of dopamine also had attenuation and enhancement effects on the excitatory response of striatal neurons to cortical stimulation. The results suggest that the attenuation and enhancement of the excitatory responses of striatal neurons to cortical stimulation which resulted from nigral conditioning stimulation is mediated by nigrostriatal dopaminergic neurons. 相似文献
10.
In the present work we have studied the postnatal development of functional dopamine, opioid and tachykinin receptors, which regulate cholinergic activity in the neostriatum. The release of endogenous acetylcholine from rat striatal slices was measured using a chemiluminescent method. We have observed that the inhibition mediated by dopamine through D 2 receptors was not detectable until postnatal day 10, whereas the inhibition mediated by opioid receptors was detectable at postnatal day 15 for δ-receptors ([D-Pen 2, D-Pen 5]-enkephalin) and at postnatal day 21 for μ-receptors ([D-Ala 2, Gly(ol) 5]-enkephalin). Excitatory effect mediated by tachykinins through NK 1 ([Sar 9, Met(O2) 11]-Substance P), NK 2 ([Nle 10]-Neurokinin A 4–10), or NK 3 (senktide) receptors was already detectable at postnatal day 5. In order to examine the influence of dopamine in the development of tachykinin and opioid systems in the neostriatum, we induced dopamine deficiency by intraventricular injection of 6-hydroxydopamine at postnatal day 3. We observed an increase in senktide-evoked acetylcholine release at postnatal day 30. The effect produced by [Sar9, Met(O211]-Substance P and [Nle10]-Neurokinin A4–10 was not modified. Furthermore, at postnatal day 35, we could observed that the two opioid receptor agonists have no effect. Our results show that dopamine, tachykinins and opioids are already able to mediate the modulation of acetylcholine release in early stages of development with a different pattern of postnatal development. Furthermore, the integrity of a dopaminergic system plays an important role in the functional development of the neostriatal cholinergic neurons which are differentially modulated by opioids or tachykinins. 相似文献
11.
Submerged rat hippocampal slices were exposed to hypoxic medium prepared with 95% N 2/5% CO 2. The population spikes recorded from CA1 cell layer were completely blocked within a range of 5–10 min. The adenosine antagonist theophylline (100 μM) delayed and partially prevented the hypoxia-induced depression. Increasing concentrations of the more potent adenosine antagonist 8-phenyltheophylline (8-PT; 0.1, 1, 10 μM) resulted in progressively less hypoxia-induced depression. The antidromically elicited afterpotentials recorded in the absence of synaptic transmission in low calcium, high magnesium medium were blocked within 8 min of hypoxia. Theophylline (100 μM) and 8-PT (10 μM) delayed to a similar extent the hypoxia-induced depression of the first afterpotential but did not prevent its complete depression. 相似文献
12.
Injections of the D 2 receptor antagonists haloperidol (0.5–8 mg/kg) and metoclopramide (6.25–50 mg/kg) in rats resulted in a dose dependent induction of Fos-like-immunoreactivity in the rostral portion of the entopeduncular nucleus (EPN) and in the medial portion of the pars reticulata of the substantia nigra (SNpr). Nigral staining occurred exclusively in neurons which were not immunoreactive for tyrosine hydroxylase and could be antagonized by pretreatment with the anticholinergic drug scopolamine (3 mg/kg). Effects were much less pronounced following injections of the selective D1 antagonist SCH-23390 (2–8 mg/kg). No staining could be observed following administration of the 5HT 3 antagonist MDL-72222 (10 mg/kg) or the 5HT 1/5HT 2 antagonist metergoline (5 mg/kg), suggesting that the effects observed with dopamine antagonists were not secondary to actions at serotonin receptors. These results are consistant with the hypothesis that blockade of dopamine receptors results in a disinhibition of cells within the SNpr and EPN and further suggest that examination of immediate-early gene expression may provide a useful tool for studying the extrastriatal circuitry engaged by manipulations of dopaminergic transmission. 相似文献
13.
The identity of the receptors involved in mediating the depressant actions of adenosine and its analogs on the spontaneous firing of rat cerebral cortical neurons was elucidated by evaluating the effects of selective A 1 and A 2 receptor agonists and antagonists. The A 1 agonist N6-cyclopentyladenosine (CPA) and the A 2 agonist CGS 21680 both depressed cortical neuronal firing. At low doses (0.001–0.01 mg/kg) the A 1 antagonist DPCPX blocked the effects of CPA, but not those of CGS 21680. At higher doses, it antagonized both agonists. The A 2 antagonist CGS 15943 (0.01–0.1 mg/kg) selectively blocked the actions of CGS 21680. At 1 mg/kg it also antagonized the responses of some neurons to CPA. These results suggest that the depressant actions of adenosinergic agonists on the firing of rat cerebral cortical neurons involve both A 1 and A 2 receptors. 相似文献
14.
Carbamylcholine stimulated [ 3H]inositol phosphate accumulation in mouse cerebral cortical slices with an ED 50 value of approximately 70 μM. Increasing concentrations of the M 2 selective muscarinic cholinergic receptor antagonist, AF-DX 116 (0.3–3.0 μM), produced parallel shifts to the right for concentration-response curves to carbamylcholine. A pA 2 value for AF-DX 116 of 6.5 (low affinity) was obtained frommSchild plot analysis. It is concluded that the M 2 muscarinic receptor subtype, as defined by high affinity [ 3H]AF-DX 116 radioligand binding, is not appreciably coupled to polyphosphoinositide hydrolysis in the mouse cerebral cortex. 相似文献
15.
Unilateral 6-hydroxydopamine (6-OHDA) lesions of substantia nigra pars compacta (SNPC) neurons in rats induce behavioural hypersensitivity to dopaminergic agonists. However, the role of specific dopamine receptors is unclear, and potential alterations in their transduction mechanisms remain to be evaluated. The present study addressed these issues employing the dopaminergic agonist, quinelorane, which efficaciously stimulated G-protein activation (as assessed by [ 35S]GTPγS binding) at cloned hD 2 (and hD 3) receptors. At rat striatal membranes, dopamine stimulated [ 35S]GTPγS binding by 1.9-fold over basal, but its actions were only partially reversed by the selective D 2/D 3 receptor antagonist, raclopride, indicating the involvement of other receptor subtypes. In contrast, quinelorane-induced stimulation (48% of the effect of dopamine) was abolished by raclopride, and by the D 2 receptor antagonist, L741,626. Further, novel antagonists selective for D 3 and D 4 receptors, S33084 and S18126, respectively, blocked the actions of quinelorane at concentrations corresponding to their affinities for D 2 receptors. Quinelorane potently induced contralateral rotation in unilaterally 6-OHDA-lesioned rats, an effect abolished by raclopride and L741,626, but not by D 3 and D 4 receptor-selective doses of S33084 and S18126, respectively. In functional ([ 35S]GTPγS) autoradiography experiments, quinelorane stimulated G-protein activation in caudate putamen and, to a lesser extent, in nucleus accumbens and cingulate cortex of naive rats. In unilaterally SNPC-lesioned rats, quinelorane-induced G-protein activation in the caudate putamen on the non-lesioned side was similar to that seen in naive animals (50% stimulation), but significantly greater on the lesioned side (80%). This increase was both pharmacologically and regionally specific since it was reversed by raclopride, and was not observed in nucleus accumbens or cingulate cortex. In conclusion, the present data indicate that, in rat striatum, the actions of quinelorane are mediated primarily by D 2 receptors, and suggest that behavioural hypersensitivity to this agonist, induced by unilateral SNPC lesions, is associated with an increase in D 2, but not D 3 or D 4, receptor-mediated G-protein activation. 相似文献
16.
In this study we have used whole-cell, voltage-clamp procedures to determine the effects of angiotensin II (AII) on net outward current (I no) in neurons co-cultured from the hypothalamus and brainstem of 1-day-old rats. I no is the sum of all inward and outward membrane currents (minus Na +, which is blocked by tetrodotoxin) which occur during the repolarization phase of the action potential. We have determined that AII elicits two separate effects on I no in cultured neurons. AII caused a reversible and concentration (0.1 nM–10 μM)-dependent increase in I no. This effect is inhibited by the AT 2 receptor-selective antagonists, PD123177 and PD123319 (both 100 nM), but not by the AT 1-selective receptor blocker, DuP753 (Losartan; 100 nM), and so it is mediated by AT 2 receptors. In a smaller number of neurons AII induced a reversible and concentration (0.01 nM–10 μM)-dependent decrease in I no that was blocked by Losartan (100 nM) but not by PD123177 (100 nM). Thus the decrease in I no is mediated by AT 1 receptors. Additionally, some neurons displayed both AT 1- and AT 2 receptor-mediated effects on I no. Our results demonstrate two distinct actions of AII on membrane ionic currents in cultured neurons, effects that are mediated by different AII receptor subtypes. 相似文献
17.
Cortical electrical stimulation has been shown to induce dense and widespread Fos expression throughout the ipsilateral and contralateral striatum. This raises interest for studying the mechanisms underlying the regulation of striatal neuron activity by cortical afferents, and for elucidating the interactions with other systems. However, the receptors mediating cortical-stimulation-induced expression of Fos in striatal neurons have not been identified. This was studied in the work reported here by stimulating the cortex after administration of glutamate or dopamine receptor antagonists, or after 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal dopaminergic system. Pretreatment with the non-competitive N-methyl- d-aspartate (NMDA) glutamate receptor antagonist MK-801 led to a marked reduction in the stimulation-induced density of Fos-immunoreactive nuclei in both the medial (about 80% reduction) and lateral (about 50–60% reduction) striatum. Preadministration of the D 1-selective dopamine antagonist SCH-23390 alone or in combination with the D 2-selective dopamine antagonist eticlopride led to a reduction in the stimulation-induced density of Fos-positive nuclei of about 60–65% in the lateral striatum, but no significant change in the medial region. The effects of 6-OHDA lesion were less pronounced, and the stimulation-induced density of Fos-immunoreactive nuclei decreased by only about 25% in the lateral region. These results indicate that both dopamine and NMDA glutamate receptors are involved in the induction of Fos by cortical stimulation, and support the hypothesis that cortex-dopamine interactions in the lateral striatum may be functionally different from those in the medial striatum. 相似文献
18.
Our previous studies have demonstrated that LY171555 (quinpirole), a specific dopamine (DA) D 2-receptor agonist, has a pressor effect in the conscious rat which is accompanied by increased sympathetic outflow and arginine vasopressin release. To test the hypothesis that LY171555 inhibits in vivo release of DA and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), from central dopaminergic neurons of the conscious, freely moving rat by activation of presynaptic DA receptors in the central nervous system and that this mechanism may be altered in the desoxycorticosterone acetate (DOCA)/NaCl model of hypertension, we used the in vivo push-pull perfusion method to study the effect of LY171555 on central DA release in normotensive and DOCA/NaCl-hypertensive rats. Levels of the DOPAC and HVA were measured in striatal perfusates by HPLC before and after administration of LY171555 (1 mg/kg, i.v.) of conscious, unrestrained 4-week DOCA/NaCl hypertensive and uninephrectomized H 2O control rats. There were no significant differences in basal striatal HVA (80 ± 12 vs 89 ± 11 pg/min; DOCA/NaCl vs control) or DOPAC levels (37 ± 5 vs 17 pg/min; DOCA/NaCl vs control) during the entire 240-min collection period. LY171555 significantly reduced HVA and DOPAC levels in perfused striatum in both normotensive control and DOCA/NaCl-hypertensive rats. The LY 17555-induced suppression in HVA levels was significantly greater in DOCA/NaCl rats (Δ = 60.7 ± 3.6%) than in H 2O controls (Δ = 49.0 ± 3.5%, P < 0.05). Pretreatment with metoclopramide (10 mg/kg, i.v.), a specific central and peripheral DA D 2-receptor antagonist, completely blocked the suppressive effects of LY171555 on HVA and DOPAC levels. These observations provide direct evidence for the presence of functionally significant presynaptic inhibitory DA D 2-receptors which modulate dopaminergic neuro-transmission in the striatum of conscious, freely moving rats. This regulatory mechanism appears to be altered in the DOCA/NaCl model of hypertension. These results support the concept that DOCA/NaCl-hypertensive rats have altered central dopaminergic activity. 相似文献
19.
Both inhibitory GABAergic and excitatory glutamatergic inputs to supraoptic nucleus (SON) neurons can influence the release of vasopressin and oxytocin. Acetylcholine is known to excite SON neurons and to increase vasopressin release. The functional significance of cholinergic receptors, located at the presynaptic nerve terminals, in the regulation of the excitability of SON neurons is not fully known. In this study, we determined the role of presynaptic cholinergic receptors in regulation of the inhibitory GABAergic inputs to the SON neurons. The magnocellular neurons in the rat hypothalamic slice were identified microscopically, and the spontaneous miniature inhibitory postsynaptic currents (mIPSCs) were recorded using the whole-cell voltage-clamp technique. The mIPSCs were abolished by the GABA A receptor antagonist, bicuculline (10 μM). Acetylcholine (100 μM) significantly reduced the frequency of mIPSCs of SON neurons from 3.59±0.36 to 1.62±0.20 Hz ( n=37), but did not alter the amplitude and the decay time constant of mIPSCs. Furthermore, the nicotinic receptor antagonist, mecamylamine (10 μM, n=13), eliminated the inhibitory effect of acetylcholine on mIPSCs of SON neurons. The muscarinic receptor antagonist, atropine (100 μM), did not alter significantly the effect of acetylcholine on mIPSCs in most of the 17 SON neurons studied. These results suggest that the excitatory effect of acetylcholine on the SON neurons is mediated, at least in part, by inhibition of presynaptic GABA release. Activation of presynaptic nicotinic receptors located in the GABAergic terminals plays a major role in the cholinergic regulation of the inhibitory GABAergic input to SON neurons. 相似文献
20.
In superfused slices of rat striatum, nicotine-evoked release of endogenous 3,4-dihydroxyphenylalanine (DOPA) was studied in comparison with that of dopamine (DA). (if(±)-Nicotine (0.1–10 μM) constantly and repetitively released DOPA and DA over a similar time course in a concentration-dependent manner. The ratio of DOPA and DA evoked was approximately 1:2–3. The turnover rate of DOPA was about 300 times higher compared to DA. (±)-Nicotine (10 μM)-induced DOPA release was mecamylamine (20 μM)-sensitive, Ca 2+-dependent and tetrodotoxin (0.3 μM)-insensitive. The (+)-isomer induced no DOPA release. These characteristics of DOPA release were almost the same as those of DA. Nicotine evokes endogenous DOPA via nicotinic cholinergic receptors in a manner similar to the transmitter DA. These findings further support a probable role of DOPA as a neuroactive substance in the rat central nervous system. 相似文献
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