Localized thermonuclear bursts from accreting magnetic white dwarfs.

Nova explosions are caused by global thermonuclear runaways triggered in the surface layers of accreting white dwarfs1-3. It has been predicted4-6 that localized thermonuclear bursts on white dwarfs can also take place, similar to type-I X-ray bursts observed in accreting neutron stars. Unexplained rapid bursts from the binary system TV Columbae, in which mass is accreted onto a moderately strong magnetized white dwarf from a low-mass companion, have been observed on several occasions in the past 40 years7-11. During these bursts, the optical/ultraviolet luminosity increases by a factor of more than three in less than an hour and fades in around ten hours. Fast outflows have been observed in ultraviolet spectral lines7, with velocities of more than 3,500 kilometres per second, comparable to the escape velocity from the white dwarf surface. Here we report on optical bursts observed in TV Columbae and in two additional accreting systems, EI Ursae Majoris and ASASSN-19bh. The bursts have a total energy of approximately 10-6  times than those of classical nova explosions (micronovae) and bear a strong resemblance to type-I X-ray bursts12-14. We exclude accretion or stellar magnetic reconnection events as their origin and suggest thermonuclear runaway events in magnetically confined accretion columns as a viable explanation.

Structure of the Circumnuclear Region of Seyfert 2 Galaxies Revealed by Rossi X-Ray Timing Explorer Hard X-Ray Observations of NGC 4945.

NGC 4945 is one of the brightest Seyfert galaxies on the sky at 100 keV, but is completely absorbed below 10 keV; its absorption column is probably the largest that still allows a direct view of the nucleus at hard X-ray energies. Our observations of it with the Rossi X-Ray Timing Explorer (RXTE) satellite confirm the large absorption, which for a simple phenomenological fit using an absorber with solar abundances implies a column of 4.5+0.4-0.4x1024 cm(-2). Using a more realistic scenario (requiring Monte Carlo modeling of the scattering), we infer the optical depth to Thomson scattering of approximately 2.4. If such a scattering medium were to subtend a large solid angle from the nucleus, it should smear out any intrinsic hard X-ray variability on timescales shorter than the light-travel time through it. The rapid (with a timescale of approximately 1 day) hard X-ray variability of NGC 4945 discovered by us with RXTE implies that the bulk of the extreme absorption in this object does not originate in a parsec-size, geometrically thick molecular torus. Instead, the optically thick material on parsec scales must be rather geometrically thin, subtending a half-angle less than 10 degrees, and it is likely to be the same disk of material that is responsible for the water maser emission observed in NGC 4945. Local number counts of Seyfert 1 and Seyfert 2 galaxies show a large population of heavily obscured active galactic nuclei (AGNs) which are proposed to make up the cosmic X-ray background (CXRB). However, for this to be the case, the absorption geometry in the context of axially symmetric unification schemes must have the obscuring material subtending a large scale height-contrary to our inferences about NGC 4945-implying that NGC 4945 is not a prototype of obscured AGNs postulated to make up the CXRB. The small solid angle of the absorber, together with the black hole mass (of approximately 1.4x106 M( middle dot in circle)) from megamaser measurements, allows a robust determination of the nuclear luminosity, which in turn implies that the source radiates at approximately 10% of the Eddington limit.

Biochemical evidence for the regulation of central noradrenergic activity by 5-HT1A and 5-HT2 receptors: microdialysis studies in the awake and anaesthetized rat.

Here we have studied the effect of various 5-HT1A and 5-HT2 receptor-selective drugs on noradrenaline release in the hippocampus on anaesthetized and awake rats using microdialysis. In the anaesthetized rat, administration of the 5-HT1A agonists buspirone, gepirone and ipsapirone increased noradrenaline levels in the microdialysates. However, the common metabolite of these compounds, 1-PP (an alpha-2 adrenoceptor antagonist with low affinity for 5-HT1A receptors), also increased noradrenaline efflux whilst the 5-HT1A receptor agonist 8-OH-DPAT and MDL 73005EF, which are not metabolized to 1-PP, did not. In the awake rat, buspirone but also 8-OH-DPAT increased noradrenaline efflux. A similar effect was observed in response to MDL 73005EF and the 5-HT1A ligand NAN-190. Since the latter two drugs have weak intrinsic activity at the post-versus presynaptic 5-HT1A receptor, a presynaptic mechanism (inhibition of 5-HT release) was implicated. The 5-HT2 receptor may be important to this mechanism as noradrenaline increased following administration of the 5-HT2 receptor antagonists, ritanserin and ICI 170,809. In conclusion, our data indicate that there are clear differences in the effects of 5-HT1A and 5-HT2 receptor-selective drugs on noradrenaline efflux in hippocampus of the anaesthetized versus awake rat. Our findings are reconcilable with the hypothesis that in the awake (but not anaesthetized) rat, release of noradrenaline in hippocampus is influenced by an inhibitory tone mediated via 5-HT2 receptors. If this inhibitory tone is removed, either by decreasing 5-HT release through activation 5-HT1A autoreceptors or by blocking postsynaptic 5-HT2 receptors, noradrenaline release increases.

In vivo monoamine release during naloxone-precipitated morphine withdrawal.

There is much evidence from animal work suggesting that the release of noradrenaline (NA) in the brain increases during naloxone-precipitated morphine withdrawal, but the evidence in favour of changes in release of 5-hydroxytryptamine (5-HT) and dopamine (DA) is contradictory. Here we demonstrate, using in vivo microdialysis, that whilst there is a considerable increase (300%) in release of NA in hippocampus precipitated by naloxone in morphine-dependent rats, there is no change in the release of either 5-HT (in hippocampus) or DA (in nucleus accumbens). These results are consistent with suggestions that the symptoms of morphine withdrawal in rats are due primarily to an increase in central NA release.

Evidence that 5-HT2 receptor activation decreases noradrenaline release in rat hippocampus in vivo.

1. Recent electrophysiological studies have shown that 5-HT2/5-HT1C receptor agonists inhibit the electrical activity of noradrenergic neurones in the rat locus coeruleus. Here we examine the effect of various agonists and antagonists of 5-HT2/5-HT1C receptors on noradrenaline release in hippocampus of anaesthetized rats using microdialysis. 2. Subcutaneous administration of the 5-HT2/5-HT1C receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI: 0.2 and 0.5 mg kg-1), caused a marked decrease (50% of pre-drug levels 60 min after injection) of noradrenaline in hippocampal dialysates which was long-lasting (greater than 120 min). Noradrenaline output also decreased in response to administration of the structural analogue of DOI, 1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane (DOB: 1 mg kg-1, s.c.). 3. The effect of DOI on noradrenaline output was prevented by pretreatment with the 5-HT2/5-HT1C receptor antagonist, ritanserin (0.4 mg kg-1, s.c.). Spiperone (0.2 and 1 mg kg-1, s.c.), a 5-HT2/dopamine D2 receptor antagonist which has low affinity for 5-HT1C receptors, also antagonized the effect of DOI (0.5 mg kg-1, s.c.). Sulpiride (50 mg kg-1, s.c.), a dopamine D2 receptor antagonist did not alter the response to DOI (0.5 mg kg-1, s.c.). 4. Both the non-selective 5-HT receptor agonist, quipazine (1 mg kg-1, s.c.), and the 5-HT-releasing agent, p-chloroamphetamine (2 mg kg-1, s.c.), decreased noradrenaline release in hippocampus and these effects were antagonized by pretreatment with ritanserin (0.4 mg kg-1, s.c.).5. Our data suggest that in vivo, noradrenaline release in hippocampus is inhibited by 5-HT2 receptor activation. This effect is probably associated with a decrease in noradrenergic neuronal activity.

Effect of naloxone-precipitated morphine withdrawal on noradrenaline release in rat hippocampus in vivo.

Here we investigated the effect of naloxone-precipitated morphine withdrawal on the release of noradrenaline in hippocampus of the anaesthetised rat. Naloxone (1 mg/kg i.p.) injected 3 and 24 h, but not 3 weeks, after eight daily injections of morphine, induced an immediate increase in hippocampal noradrenaline release. This striking effect of naloxone was markedly attenuated by pretreatment with clonidine (0.1 mg/kg s.c.). These findings provide direct evidence for a marked release of noradrenaline in hippocampus during opiate withdrawal in vivo.

Clonidine but not nifedipine prevents the release of noradrenaline during naloxone-precipitated opiate withdrawal: an in vivo microdialysis study in the rat.

In this study we have examined whether the alpha 2-adrenoceptor agonist clonidine and the calcium channel antagonist nifedipine firstly inhibit the naloxone-precipitated withdrawal syndrome in morphine-dependent rats and secondly reduce central noradrenaline release during withdrawal. We demonstrate that both clonidine (0.1 mg/kg) and nifedipine (10 mg/kg) attenuate the naloxone-precipitated withdrawal syndrome. Using in vivo microdialysis, we demonstrate that following naloxone the release of noradrenaline, as measured by perfusates from hippocampus, increases 300% in morphine-dependent rats. However, whilst pretreatment with clonidine inhibited this increased noradrenaline release, nifedipine did not. These findings suggest that whilst the action of clonidine in attenuating the morphine withdrawal syndrome may be mediated by decreasing central noradrenaline release, this is not the mechanism by which nifedipine acts.