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At least 523 records · Page 29Linked to original sources
PubMed1994

Activation of adenosine A1 and A2 receptors differentially modulates calcium channels and glycinergic synaptic transmission in rat brainstem.

Multiple types of calcium channels are responsible for calcium influx that triggers transmitter release in the mammalian CNS. To test the contribution of each calcium channel type on synaptic modulation, we recorded calcium currents from somata of presynaptic interneurons and unitary glycinergic postsynaptic currents in the rat brainstem. In interneuron somata, A1 receptor activation inhibited predominantly N-type (omega-conotoxin GVIA-sensitive) and, to a lesser extent, P-type (omega-agatoxin IVA-sensitive) channels. At the presynaptic terminal, N- and P-type channels mediated synaptic transmission. omega-CgTx occluded synaptic inhibition by A1 receptor activation, suggesting that synaptic inhibition was mediated predominantly by N-type channel inhibition. A2 receptor activation facilitated synaptic transmission, probably through potentiation of P-type channels at the presynaptic terminal.

Adenosine↗
PubMed2002

Developmental profiles of glutamate receptors and synaptic transmission at a single synapse in the mouse auditory brainstem.

Using whole-cell recordings from presynaptic terminals and postsynaptic principal neurons in the mouse medial nucleus of the trapezoid body (MNTB), we have characterized properties of the calyx of Held synapse during the first three postnatal weeks. We observed that evoked excitatory postsynaptic currents (EPSCs) mediated by NMDA receptors (NMDAR) increased until postnatal day 11/12 (P11/12) after which they declined to very low or undetectable levels at P16. Meanwhile, EPSCs mediated by AMPA receptors (AMPAR) showed an approximate three-fold increase in amplitude. These changes were paralleled by NMDAR and AMPAR currents evoked by exogenous NMDA and kainate to MNTB neurons except that whole-cell kainate currents remained constant after P7/8 while AMPAR-EPSCs continued to increase. We found that the decay time constant tau for NMDAR-EPSCs and AMPAR-EPSCs declined by about 30 % and 70 %, respectively. Analyses of NMDAR-EPSCs with subunit-specific pharmacological agents including ifenprodil, N,N,N',N'-tetrakis(2-pyridylmethyl)-ethylenediamine (TPEN), zinc and Mg(2+) revealed subtle developmental changes in subunit composition. As maturation progressed, this synapse displayed a reduction in the number of presynaptic spike failures and the extent of synaptic depression in response to trains of stimuli (50-300 Hz) while the recovery rate from depression accelerated. These results demonstrate profound changes in the size and kinetics of postsynaptic glutamate receptors and in the spike-firing capability of presynaptic terminals at the calyx of Held-MNTB synapse during early development. We suggest that these concurrent presynaptic and postsynaptic adaptations represent important steps for synapse consolidation and refinement and ultimately for the development of fast high-fidelity transmission at this synapse.

Aging↗
PubMed2005

Axonal dynactin p150Glued transports caspase-8 to drive retrograde olfactory receptor neuron apoptosis.

Olfactory receptor neurons (ORNs) undergo caspase-mediated retrograde apoptosis after target removal (bulbectomy), in which axonal caspase-9 and caspase-3 activation leads to terminal apoptosis in ORN soma of the olfactory epithelium. Here, we show that caspase-8 can act as an initiator of ORN apoptosis after bulbectomy and also after synaptic instability is induced by NMDA-mediated excitotoxic death of ORN target neurons in the olfactory bulb. Caspase-8 and caspase-3 are sequentially activated within ORN presynaptic terminals, and caspase-8 complexes with dynactin p150Glued, (a retrograde motor protein) and is transported retrogradely, preceding axonal caspase-3 activation and apoptosis of ORN cell bodies. Focal in vivo inhibition of initiator caspase activation or microtubule-dependent transport (with Taxol) at the lesioned axon terminus results in a significant reduction in retrograde axonal caspase-8 and caspase-3 activation and inhibition of retrograde ORN death. Caspase-8 activation and retrograde transport after NMDA lesion is similarly reduced in mice null for p75, the low-affinity nerve growth factor receptor. The retrograde apoptosis of ORNs thus involves a novel mechanism that used p75 in the local activation of caspase-8. Once caspase-8 is maximally activated in the presynaptic terminal, it is transported retrogradely by the motor complex dynactin/dynein, a process that can be inhibited focally to inhibit ORN apoptosis after acute axonal lesion. These data have revealed a novel mechanism of retrograde apoptosis, in which caspase-8 complexes directly with axonal dynactin p150Glued to reveal a differential vulnerability of subpopulations of ORNs to undergo apoptosis after axonal damage and the loss of olfactory bulb target neurons.

Acetylcholine↗
PubMed1987

Facilitation of serotonin (5-HT) release in the rat brain cortex by cAMP and probable inhibition of adenylate cyclase in 5-HT nerve terminals by presynaptic alpha 2-adrenoceptors.

Stimulation-evoked tritium overflow was examined in superfused rat brain cortex slices (stimulus: electrical impulses; 3 Hz) and synaptosomes (stimulus: potassium 12 mmol/l) preincubated with 3H-5-HT. 1. In slices and synaptosomes, the evoked 3H overflow was facilitated by forskolin and 8-Br-cAMP, but was not affected by AH 21-132 (an inhibitor of cAMP phosphodiesterase; cis-6-(p-acetamidophenyl)-1,2,3,4,4a,10b-hexahydro-8,9-dimethoxy-2-methylbenzo [c] [1,6]-naphthyridine). In the presence of AH 21-132, the facilitatory effect of forskolin on evoked overflow was increased. 2. In slices, AH 21-132 or combined administration of forskolin plus AH 21-132 did not change the percentage of basal or evoked 3H overflow represented by unmetabolized 3H-serotonin (about 30% and 60%, respectively). 3. In slices, cocaine or 6-nitroquipazine, an inhibitor of serotonin uptake, did not influence the increase in evoked overflow produced by forskolin plus AH-21-132. Forskolin plus AH 21-132 did not alter the inhibitory effect of serotonin (examined in the presence of 6-nitroquipazine) and the facilitatory effect of metitepin (a serotonin receptor antagonist) on evoked 3H overflow, but considerably decreased the inhibitory effect of clonidine or B-HT 920 (2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo-[5,4-d]-azepine). The present results suggest that the serotoninergic nerve terminals in the rat brain cortex are endowed with an adenylate cyclase, which is negatively coupled to the presynaptic alpha 2-adrenoceptors, but is not linked to the presynaptic autoreceptors.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1991

Synaptogenesis in the rat suprachiasmatic nucleus: a light microscopic immunocytochemical survey.

MabQ155, a monoclonal antibody against synaptophysin, has been used to conduct a light microscopic survey of synaptogenesis in the suprachiasmatic nucleus of the perinatal rat. Synaptophysin is an integral component of synaptic vesicle membranes which is expressed in growth cones and growth cone filopodia as well as in mature synapses. With the light microscope, mabQ155 immunoreactivity in growth cones can be distinguished from that in presynaptic terminals on the basis of the size of immunoreactive puncta. The current study presents a qualitative and quantitative analysis of synaptogenesis from the day of birth (P0) to postnatal day 10 (P10). In our quantitative analysis we have used daily intervals during the first postnatal week, distinguished between growth cones and presynaptic terminals, and divided the suprachiasmatic nucleus into sampling regions that are related to the progress of synaptogenesis. Our data demonstrate regional differences in synaptogenesis within the suprachiasmatic nucleus (SCN), document the temporal progression from the penetration of growth cones to the appearance of mature synapses, and provide information about gradients of synaptogenesis in the nucleus during development.

Aging↗
PubMed1999

Neurons and their dendrites in frontotemporal dementia.

Regional and areal patterns of cell vulnerability (manifested as cell death and neuron loss) and cell sensitivity (as revealed by the presence of intracytoplasmic inclusions) are described in patients with frontotemporal dementia (FTD) and FTD+ motor neuron disease (MND). This is followed by studies geared to learning about possible mechanisms involved in selective neuron loss and studies focused on recognizing the identity of vulnerable populations of local-circuit neurons and the impact of FTD on individual cells as well as on postsynaptic and presynaptic terminals in the frontal cortex. Neuron loss is not associated with increased vulnerability to nuclear DNA fragmentation, and nor is it accompanied by modifications in the expression of the proteins Bcl-2 and Bax, and transcription factors c-Fos and c-Jun, thus suggesting that these proteins are probably not involved in cell death in these disorders. In the frontal and temporal cortices, glutamatergic pyramidal cells and calbindin-D28k-immunoreactive GABAergic local-circuit neurons are lost in the upper cortical layers. Parvalbumin-immunoreactive cells are preserved. In addition, reduction of putative postsynaptic sites (as inferred from the decreased numbers of dendritic branches in both pyramidal and nonpyramidal neurons, and of dendritic spines in pyramidal cells) in remaining neurons of the upper layers, as well as reduction of presynaptic terminals (as suggested by the decreased expression of synaptic vesicle-associated proteins, synaptophysin, synaptotagmin, rab 3a and synapsin 1, and presynaptic plasma membrane proteins SNAP-25 and syntaxin 1) in the upper layers of the frontal cortex, but not of the posterior parietal cortex, demonstrate the combined devastating effects of FTD on cortico-cortical connections.

Biomarkers↗
PubMed1997

The soluble N-ethylmaleimide-sensitive factor attached protein receptor complex in growth cones: molecular aspects of the axon terminal development.

Soluble N-ethylmaleimide-sensitive factor attached protein (SNAP) receptor (SNARE) mechanisms are thought to be involved in two important processes in axonal growth cones: (1) membrane expansion for axonal growth and (2) vesicular membrane fusion for mature synaptic transmission. We investigated the localization and interactions among the proteins involved in SNARE complex formation in isolated growth cone particles (GCP) from forebrain. We demonstrated that the SNARE complex is present in GCPs morphologically without synaptic vesicles (SVs) and associated with growth cone vesicles. However, the apparently SV-free GCP was lacking in the regulatory mechanisms inhibiting SNARE complex formation proposed in SV fusion, i.e., the association of synaptotagmin with the SNARE complex, and vesicle-associated membrane protein (VAMP)-synaptophysin complex formation. The core components of the SNARE complex (syntaxin, SNAP-25, and VAMP) accumulated for several days before postnatal day 7, when SVs first appeared, and preceded the accumulation of marker proteins such as synaptophysin, SV2, and V-ATPase. Our present results suggest that the SNARE mechanism for vesicular transmitter release is not fully functional in growth cones before the appearance of SVs, but the SNARE mechanism is working for membrane expansion in growth cones, which supports our recent report. We concluded that the regulation of the SNARE complex in growth cones is different from that in mature presynaptic terminals and that this switching may be one of the key steps in development from the growth cone to the presynaptic terminal.

Animals↗
PubMed1987

Differential effects of calcium entry blockers on pre- and postsynaptic influx of calcium in the rat hippocampus in vitro.

A decrease in extracellular free Ca ([Ca2+]o) in response to stimulation of Schaffer collaterals could be recorded in or near the stratum pyramidale even when synaptic transmission was completely blocked. Under the same conditions, alvear stimulation also evoked a decrease in [Ca2+]o at the same site. We attributed the former to influx of Ca2+ into presynaptic terminals and the latter to influx into postsynaptic (pyramidal) cells. Both pre- and postsynaptic Ca2+ influx were completely blocked by Ni2+ (2.5 mM). Nifedipine (5-10 microM). verapamil (50-100 microM) and fendiline (100-200 microM) reduced the postsynaptic influx of Ca2+ but did not alter Ca2+ loss from the extracellular space into presynaptic terminals. The calcium channel activators, BAY-K 8644 and CGP 28,392, had no consistent effect on either pre- or postsynaptic influx. Occasional enhancement of both pre- and postsynaptic responses was seen. In most studies the agents were without effect and on occasions a reduction in both responses was seen. The results could indicate that Ca-channels at pre- and postsynaptic sites in CA1 may be of different types.

Action Potentials↗
PubMed2003

Modulation of inhibitory synaptic activity by a non-alpha4beta2, non-alpha7 subtype of nicotinic receptors in the substantia gelatinosa of adult rat spinal cord.

The GABA/glycine-mediated inhibitory activity in the substantia gelatinosa (SG) of the spinal cord is critical in the control of nociceptive transmission. We examined whether and how SG inhibitory activity might be regulated by neuronal nicotinic receptors (nAChRs). Patch-clamp recordings were performed in SG neurons of spinal slice preparations from adult rats. We provided electrophysiological evidence that inhibitory presynaptic terminals in the SG expressed nAChRs and their activation resulted in large increases in the frequency of spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) in over 90% SG neurons tested. The enhancement of inhibitory activity was mediated by increases in the release of GABA/glycine, and direct Ca(2+) entry through SG presynaptic nAChRs appeared to be involved. Miniature IPSC frequency could be enhanced by the nAChR agonists nicotine or cytisine. Nicotine could still elicit large increases in mIPSC frequency in the presence of the alpha4beta2 nAChR antagonist dihydro-beta-erythroidine (5 microM) and the alpha7 nAChR-selective antagonist methyllycaconitine (40 nM). However, nicotine did not produce a significant enhancement of mIPSC frequency in the presence of the broad spectrum nAChR antagonist mecamylamine (5 microM). Nicotinic agonist-evoked whole-cell currents from SG neurons and the antagonist profiles also indicated the presence of a subtype of nAChRs, which were different from the major central nervous system nAChR subtypes, i.e. alpha4beta2* or alpha7 nAChRs. Together, our results suggest that a subtype of nAChR, possibly alpha3beta4* nAChR or a new nAChR type, is highly expressed at the inhibitory presynaptic terminals in SG of adult rats and play a role in the control of inhibitory activity in SG.

2-Amino-5-phosphonovalerate↗
PubMed1979

Synaptic terminal parameters in unanesthetized rat cerebral cortex.

The ultrastructure of synapses from the molecular layer of parietal cortex was examined in two groups of unanesthetized rats. Rats of the first group were killed by stunning across the back of the neck, and those of the second group by the introduction of fixative through a preimplanted carotid artery cannula. Comparison of synapses from the two groups revealed that the distribution of synaptic types was the same. A larger percentage of synapses of the cannulated group has vesicle attachment sites than did those of the stunned group. The area and perimeter of the presynaptic terminals were significantly larger in synapses from the cannulated group, although the equivalent length of the postsynaptic thickening was less. The mean value for synaptic curvature was greater in the cannulated group, although over 80% of synapses in both groups had positive curvatures. No significant differences were found between the groups for the relationships between presynaptic terminal area and synaptic vesicle number, and between postsynaptic thickening length and synaptic curvature. Membrane recycling is suggested as a mechanism of accounting for the differences. The preponderance of postively-curved synapses in unanesthetized material may indicate a preponderance of functioning synapses.

Anatomy↗
PubMed1980

Fine structural studies of synaptogenesis in the superficial layers of the chick optic tectum.

Synaptogenesis in the superficial layers of the rostral pole of the optic tectum has been studied in the chick from embryonic day six (E6) to seven days post-hatching. Symmetrical membrane densities of puncta adhaerentia are observed prior to the detection of synapses and throughout development. Immature synaptic contacts are observed by E7. These early synapses are primarily axodendritic; however, somatodendritic, dendrodendritic, axosomatic and axoglial synapses are also observed. The majority of these synapses have asymmetrical membrane densities and the presynaptic terminals contain clear, spherical, synaptic vesicles. Synaptic terminals containing pleomorphic vesicles and making symmetrical synaptic contacts are not commonly observed until the third week of embryonic development, and may represent the onset of inhibitory function within the tectum. Comparison of the number of synapses per unit area in control versus experimental tecta, after unilateral eye enucleations of E3, indicates that the presynaptic terminals of some synapses present at E8 are of retinal origin. It is suggested that the development of retinotectal synapses follows a rostrocaudal gradient in the tectum and corresponds to the intrinsic tectal pattern of cytoarchitectonic differentiation.

Aging↗
PubMed2006

Developmental dissociation of presynaptic inhibitory neurotransmitter and postsynaptic receptor clustering in the hypoglossal nucleus.

At postsynaptic densities of mouse hypoglossal motoneurons, the proportion of glycine receptors co-clustered with GABAA receptors increases from neonatal to adult animals, suggesting that mixed synapses might play a greater role in adult synaptic inhibition. We visualized the presynaptic correlates of these developmental changes using immunocytochemistry. At P5, presynaptic terminals contained glycine and GlyT2 and/or GABA and GAD65, but at P15, the majority of inhibitory terminals contained glycine and GlyT2 only. The GABAergic component of evoked inhibitory postsynaptic currents in HMs decreased strongly between P5 and P15. Similarly, miniature inhibitory postsynaptic currents evolved from mainly glycinergic and mixed glycinergic/GABAergic events at P3-5 to predominantly glycinergic currents at P15. These results indicate that the decrease in the proportion of functional mixed inhibitory synapses with maturation results from a loss of the ability of presynaptic terminals to release both neurotransmitters during development while co-aggregation of GlyRs + GABAARs at postsynaptic loci remained.

Animals↗
PubMed1993

Inhibition of neurotransmitter release by C2-domain peptides implicates synaptotagmin in exocytosis.

Neurotransmitter release is triggered by Ca2+ ions binding to an unknown Ca2+ receptor within presynaptic terminals. Synaptotagmin, a Ca2(+)-binding protein of synaptic and other secretory vesicles, has been proposed to mediate vesicle-plasma membrane interactions during neurotransmitter release. Here we test this hypothesis using the giant synapse of the squid Loligo pealei, which because of its unusually large size and well established physiology is uniquely suited for dissecting presynaptic events. We find that injection of peptides from the C2 domains of synaptotagmin into squid giant presynaptic terminals rapidly and reversibly inhibits neurotransmitter release. Our data are consistent with these peptides competitively blocking release after synaptic vesicle docking and indicate that Ca2+ probably initiates neurotransmitter release by regulating the interaction of synaptotagmin with an acceptor protein.

Amino Acid Sequence↗
PubMed2002

Oxidative and nonoxidative metabolism of excited neurons and astrocytes.

There is evidence that the metabolic responses to afferent and efferent nervous activity are dissociated at sites of neuronal excitation in brain. Whether efferent activity follows afferent activity depends on the responsiveness of postsynaptic neurons, which in turn depends on the summation of excitatory and inhibitory postsynaptic potentials. The afferent activity excites the presynaptic terminals and astrocytes, whereas the efferent activity arises from excitation of the dendrites of projection neurons. Measurements in vivo indicate that primary stimulation, elicited by simple stimuli, gives rise to limited increases of energy metabolism associated with afferent activity. Reports show that a major consequence of afferent activity, in addition to the release of excitatory neurotransmitters from presynaptic terminals and the import of glutamate by astrocytes, is the establishment of rates of blood flow commensurate with increased rates of oxidative energy metabolism associated with efferent activity projecting from the site of activation. Increased flow rates overcome the inherent diffusion limitation of oxygen delivery, while increased rates of glycolysis elevate tissue pyruvate contents, to which oxygen consumption rates are matched. In vivo, neurons in the baseline condition sustain no net import of pyruvate or lactate, and the reported changes of metabolism subserving afferent and efferent activity are additive rather than linked by significant additional transfer of pyruvate or lactate from astrocytes. The dissociation of blood flow changes from efferent activity weakens the identification of functional states by changes of blood flow alone. It raises the possibility that uncoupling of flow from oxidative metabolism occurs at sites of low efferent activity, such that dissociations of flow and glycolysis from oxygen consumption signify imbalances of afferent and efferent activity.

Adenosine Triphosphate↗
PubMed1997

Synelfin regulation during the critical period for song learning in normal and isolated juvenile zebra finches.

Male zebra finches (Taeniopygia guttata) learn to sing during a critical period in adolescence. We previously described a presynaptic protein, synelfin, whose mRNA is increased early in this critical period in a brain nucleus specifically implicated in song learning, lateral MAN (lMAN). In the current study, in situ hybridization was used to map this change in gene expression to the subregion of lMAN that projects to the robust nucleus of the archistriatum (RA), the principal motor output of the telencephalic circuit that controls song production. Using confocal immunofluorescence microscopy, we detected numerous puncta of synelfin immunoreactivity that apparently represent presynaptic terminals from lMAN in the RA of young males. Synelfin immunoreactivity in RA declined abruptly between 40 and 45 days of age, a time of major synaptic reorganization in RA. This change did not occur until about 10 days after the decline in synelfin mRNA in cell bodies within lMAN, indicating a relatively slow turnover of the protein in presynaptic terminals and suggesting that some of the functional changes that occur during the critical period may arise from regulatory decisions that were initiated a week or more earlier. Depriving birds of tutoring did not halt or delay the decline of synelfin mRNA in lMAN. This change in gene expression must not be a consequence of early song learning, but may reflect an innate or programmed step in song circuit development.

Amyloid↗
PubMed2004

Effect of 4-aminopyridine on synaptic transmission in rat hippocampal slices.

Extracellular field excitatory postsynaptic potentials (fEPSPs) were recorded in area CA1 of rat hippocampal slices in vitro. The responses evoked by spontaneously released glutamate and GABA were recorded from area CA1 pyramidal neurons in rat hippocampal slices in whole-cell mode. The glutamate and GABA receptor-associated ligand-gated currents were obtained from dissociated single hippocampal pyramidal cells. The results showed that 4-aminopyridine (4-AP) had obvious effects on both presynaptic and postsynaptic events. Applications of 4-AP in micromolar concentration resulted in persistent enhancement of the initial slope of fEPSPs with the half-maximal enhancement concentration (EC(50)) of 46.7+/-2.68 microM. At the concentration of 200 microM, 4-AP increased the initial slopes of the total fEPSPs, NMDA- and AMPA-mediated fEPSPs components to 225.6+/-23.8%, 177.4+/-20.1% and 142.3+/-18.9%, respectively, but had no effect on the fiber volley. The half-maximal stimulus intensity to induce responses was reduced from 5.14+/-0.27 to 3.58+/-0.23 V. The frequencies of mEPSCs and mIPSCs were increased to 324.2+/-25.4% and 287.3+/-36.3% by 200 microM 4-AP. The amplitude histograms of mEPSCs and mIPSCs were fitted with Gaussian distributions. After 200 microM 4-AP application, the first and second peaks in Gaussian distributions of mEPSCs were shifted from 8.73+/-0.94 and 17.78+/-2.13pA to 10.48+/-0.82 and 21.14+/-2.45 pA, while those of mIPSCs were shifted from 13.65+/-0.96 and 25.51+/-2.95 pA to 11.21+/-1.04 and 23.08+/-2.37 pA. At 200 microM, 4-AP reduced paired-pulse facilitation and accelerated synaptic fatigue induced by stimulation at 10 Hz (for 1 s) and the ratio of fEPSPs(10)/fEPSPs(1) was decreased from 1.62+/-0.16 to 0.61+/-0.15. At 200 microM, 4-AP inhibited postsynaptic GABA currents induced by 5 microM GABA to 68.2+/-15.5%: by countering the effect of enhanced release of GABA from presynaptic terminals, this could depress the inhibitory pathway. Also at 200 microM, 4-AP increased NMDA currents to 155.3+/-17.8%, but had no significant effect on AMPA currents (94.2+/-15.6%). Our experimental results thus show that 4-AP-induced changes of synaptic transmission in area CA1 of rat hippocampus may be attributed to 4-AP's effects on both presynaptic terminals and postsynaptic receptors.

4-Aminopyridine↗
PubMed1999

Electrophysiology of synaptic vesicle cycling.

Patch-clamp capacitance measurements can monitor in real time the kinetics of exocytosis and endocytosis in living cells. We review the application of this technique to the giant presynaptic terminals of goldfish bipolar cells. These terminals secrete glutamate via the fusion of small, clear-core vesicles at specialized, active zones of release called synaptic ribbons. We compare the functional characteristics of transmitter release at ribbon-type and conventional synapses, both of which have a unique capacity for fast and focal vesicle fusion. Subsequent rapid retrieval and recycling of fused synaptic vesicle membrane allow presynaptic terminals to function independently of the cell soma and, thus, as autonomous computational units. Together with the mobilization of reserve vesicle pools, local cycling of synaptic vesicles may delay the onset of vesicle pool depletion and sustain neuronal output during high stimulation frequencies.

Animals↗
PubMed1997

Social isolation in the rat enhances alpha 2-autoreceptor function in the hippocampus in vivo.

This study investigated the effects of isolation rearing from weaning in rats on extracellular noradrenaline in the dorsal hippocampus in vivo, measured using microdialysis. Male Lister hooded rats were obtained at weaning and reared in social isolation or in groups for six to eight weeks. Basal noradrenaline efflux did not differ between isolation- and group-reared rats. Local K+ stimulation (50 and 100 mM) increased noradrenaline efflux in the hippocampus of both groups of rats; however, this effect was greater in group-reared rats (50 mM K+). The alpha 2-adrenoceptor agonist, clonidine (0.3 mg/kg, i.p.), reduced noradrenaline efflux in both groups of rats, but this decrease was greater in isolates. Systemic (1.0 mg/kg, i.p.) and local (via the probe; 100 microM) administration of the alpha 2-adrenoceptor antagonist, idazoxan, increased noradrenaline efflux, but these responses were also greater in isolation-reared rats. The magnitudes of the idazoxan-induced increases in noradrenaline efflux were similar for both systemic and local administration, indicating that presynaptic terminal alpha 2-adrenoceptors were predominantly involved. Furthermore, although tail pinch increased noradrenaline efflux in both isolation- and group-reared rats, there was a significant/attenuation in the response in the isolation- compared to group-reared rats. Taken together with previous findings, the present results provide evidence in favour of an isolation-induced enhancement in the function of the presynaptic terminal alpha 2-autoreceptor in the dorsal hippocampus in vivo, resulting in decreased functional responsiveness of hippocampal noradrenergic nerve terminals.

Adrenergic alpha-Agonists↗