A Single-Year Cosmic Ray Event at 5410 BCE Registered in C-14 of Tree Rings

The annual C-14 data in tree rings is an outstanding proxy for uncovering extreme solar energetic particle (SEP) events in the past. Signatures of extreme SEP events have been reported in 774/775 CE, 992/993 CE, and similar to 660 BCE. Here, we report another rapid increase of C-14 concentration in tree rings from California, Switzerland, and Finland around 5410 BCE. These C-14 data series show a significant increase of similar to 6 parts per thousand in 5411-5410 BCE. The signature of C-14 variation is very similar to the confirmed three SEP events and points to an extreme short-term flux of cosmic ray radiation into the atmosphere. The rapid C-14 increase in 5411/5410 BCE rings occurred during a period of high solar activity and 60 years after a grand C-14 excursion during 5481-5471 BCE. The similarity of our C-14 data to previous events suggests that the origin of the 5410 BCE event is an extreme SEP event.Peer reviewe

Tyrosine-induced release of dopamine is under inhibitory control of presynaptic dopamine D2 and, probably, D3 receptors in the dorsal striatum, but not in the nucleus accumbens

Item does not contain fulltextStimulation of dopamine D2-like receptors decreases extracellular dopamine in the dorsal striatum and the nucleus accumbens. It is unknown whether the role of these receptors differs from that of dopamine D3 receptors. It is also unknown to what extent the role of these two types of receptors varies across both structures. Using microdialysis, we therefore investigated whether intracerebrally administered quinpirole, a dopamine D2-like receptor agonist, and PD 128907, (S(+)−(4aR,10bR)−3,4,4a,10b−tetrahydro−4−propyl−2H,5H−[1]−benzopyrano[4,3−b]−1,4−oxazin−9−ol, a dopamine D3 receptor preferring agonist, differentially alter the tyrosine-induced increase of extracellular dopamine in the dorsal striatum and the nucleus accumbens, respectively. Perfusion of tyrosine (100 μM) into the dorsal striatum and the nucleus accumbens enhanced extracellular dopamine in a physiological manner in both areas. Infusion of the Na+ channel blocker tetrodotoxin (2 μM) suppressed the enhanced level of dopamine derived from exogenous tyrosine in both brain areas. Infusion of the dopamine D2-like receptor agonist quinpirole at a concentration (1 nM), which alone did not affect basal extracellular dopamine, reduced tyrosine-enhanced extracellular dopamine when infused into the dorsal striatum, but not into the nucleus accumbens; the preferential dopamine D3 receptor agonist, PD 128907, had similar effects. Haloperidol, a dopamine D2-like receptor antagonist, given systemically at a dose, which alone did not significantly affect basal dopamine levels (10 nmol/kg i.p.), enhanced extracellular dopamine derived from exogenous tyrosine. This haloperidol treatment antagonized only the quinpirole-induced, but not the PD 128907-induced reduction in dopamine levels seen in tyrosine-treated rats. The results show that extracellular dopamine derived from exogenous tyrosine is under inhibitory control of presynaptic dopamine D2-like receptors in the dorsal striatum, but not in the nucleus accumbens; to what extent the same holds for dopamine D3 receptors remains to be proven. Future studies are required to elucidate whether the noted difference is absolute or not

Contribution of vesicular and cytosolic dopamine to the increased striatal dopamine efflux elicited by intrastriatal injection of dexamphetamine.

Contains fulltext : 49115.pdf (publisher's version ) (Closed access)Systemic administration of high doses of dexamphetamine induces a dopamine efflux that has its intracellular origin in both the vesicular, reserpine-sensitive dopamine pool and the cytosolic, alpha-methyl-para-tyrosine-sensitive, newly synthesized dopamine pool. It remains unknown whether locally administered dexamphetamine produces similar effects. Using a brain microdialysis technique that is combined with a microinjection needle, the contribution of the vesicular and cytosolic pools to the dopamine efflux induced by striatal injection of dexamphetamine was analyzed in rats. The transient striatal dopamine efflux induced by intrastriatal injection of dexamphetamine (1.0 microg/0.5 microl) was significantly reduced by systemic administration of reserpine (5mg/kg i.p., given 24 h earlier) or alpha-methyl-para-tyrosine (250 mg/kg i.p., given 2 h earlier). The effects of dexamphetamine on the striatal dopamine were nearly nullified by combined treatment with reserpine and alpha-methyl-para-tyrosine. The sum of the amounts of extracellular dopamine that was sensitive to either reserpine or alpha-methyl-para-tyrosine, was far greater than 100%, namely 146.1% of the basal dopamine level and 144.0% of the dexamphetamine-induced dopamine level. The present study indicates that both the vesicular dopamine pool and the cytosolic dopamine pool contribute to the transient increase of striatal dopamine efflux induced by intrastriatal injection of dexamphetamine. This study also suggests that striatally applied dexamphetamine can promote the redistribution of rat striatal dopamine from vesicles to the cytosol in vivo

Endomorphin-2 and endomorphin-1 promote the extracellular amount of accumbal dopamine via nonopioid and mu-opioid receptors, respectively.

Contains fulltext : 49412.pdf (publisher's version ) (Closed access)Activation of mu-opioid receptors in the nucleus accumbens (NAc) is known to increase accumbal dopamine efflux in rats. Endomorphin-2 (Tyr-Pro-Phe-Phe-NH(2); EM-2) and endomorphin-1 (Tyr-Pro-Trp-Phe-NH(2); EM-1) are suggested to be the endogenous ligands for the mu-opioid receptor. As the ability of EM-2 and EM-1 to alter the accumbal extracellular dopamine level has not yet been studied in freely moving rats, the present study was performed, using a microdialysis technique that allows on-line monitoring of the extracellular dopamine with a temporal resolution of 5 min. A 25 min infusion of either EM-2 or EM-1 into the NAc (5, 25, and 50 nmol) produced a dose-dependent increase of the accumbal dopamine level. The EM-2 (50 nmol)- and EM-1 (25 and 50 nmol)-induced dopamine efflux were abolished by intra-accumbal perfusion of tetrodotoxin (2 muM). Intra-accumbal perfusion of the mu-opioid receptor antagonist CTOP (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Phe-Thr-NH(2); 3 nmol) failed to affect the EM-2 (50 nmol)-induced dopamine release, whereas it significantly inhibited the EM-1 (25 and 50 nmol)-induced dopamine release. The EM-1 (50 nmol)-induced accumbal dopamine efflux was significantly reduced by the systemic administration of the putative mu1-opioid receptor antagonist naloxonazine (15 mg/kg, intraperitoneally (i.p.), given 24 h before starting the perfusion). Systemic administration of the aspecific opioid receptor antagonist naloxone (1 mg/kg, i.p., given 10 or 20 min before starting the perfusion) also failed to affect the EM-2 (50 nmol)-induced dopamine efflux, whereas it significantly inhibited the EM-1 (25 and 50 nmol)-induced dopamine efflux. The present study shows that the intra-accumbal infusion of EM-2 and EM-1 increases accumbal dopamine efflux by mechanisms that fully differ. It is concluded that the effects of EM-2 are not mediated via opioid receptors in contrast to the effects of EM-1 that are mediated via mu1-opioid receptors in the NAc

Role of alpha adrenoceptors in the nucleus accumbens in the control of accumbal noradrenaline efflux: a microdialysis study with freely moving rats.

Contains fulltext : 53395.pdf (publisher's version ) (Closed access)Microdialysis technique was used to study the effects of the locally applied alpha adrenoceptor agonist phenylephrine and antagonist phentolamine on the basal noradrenaline efflux as well as on the noradrenaline uptake inhibitor desipramine-elicited noradrenaline efflux in the nucleus accumbens (NAc) of freely moving rats.Tetrodotoxin reduced basal noradrenaline efflux by 72%, whereas desipramine increased it by 204%. Phenylephrine reduced the basal noradrenaline efflux by 32% and phentolamine blocked this effect. Phentolamine elevated the basal noradrenaline efflux by 150% and phenylephrine counteracted this effect. The desipramine-elicited noradrenaline efflux was not affected by phenylephrine, but enhanced by phentolamine. Desipramine counteracted the effects of phenylephrine and potentiated those of phentolamine.These results indicate that the accumbal noradrenaline efflux is under inhibitory control of alpha adrenoceptors that are suggested to be presynaptically located on adrenergic nerve terminals in the NAc. Furthermore, this study suggests that the conformational state of alpha adrenoceptors varies across the available amount of noradrenaline. The clinical impact of these data is discussed