Dopamine increases in the nucleus accumbens after ethanol administration in rats, but the contributions of the core and shell subregions to this response are unclear. The goal of this study was to determine the effect of various doses of i.v. ethanol infusions on dopamine in these two subregions of the nucleus accumbens. Male Long-Evans rats were infused with either acute i.v. ethanol (0.5, 1.0, 1.5 g/kg), repeated i.v. ethanol (four 1.0 g/kg infusions resulting in a cumulative dose of 4.0 g/kg), or saline as a control for each condition. Dopamine and ethanol were measured in dialysate samples from each experiment. The in vivo extraction fraction for ethanol of probes was determined using i.v. 4-methylpyrazole, and was used to estimate peak brain ethanol concentrations after the infusions. The peak brain ethanol concentrations after the 0.5, 1.0 and 1.5 g/kg ethanol infusions were estimated to be 20, 49 and 57 mM, respectively. A significant dopamine increase was observed for the 0.5 g/kg ethanol group when collapsed across subregions. However, both the 1.0 g/kg and 1.5 g/kg ethanol infusions produced significant increases in dopamine levels in the shell that were significantly higher than those in the core. An ethanol dose-response effect on dopamine in the shell was observed when saline controls, 0.5, 1.0, and 1.5 g/kg groups were compared. For the cumulative-dosing study, the first, second, and fourth infusions resulted in significant increases in dopamine in the shell. However, these responses were not significantly different from one another. The results of this study show that the shell has a stronger response than the core to i.v. ethanol, that dopamine in the shell increases in a dose-dependent manner between 0.5-1.0 g/kg doses, but that the response to higher ethanol doses reaches a plateau.

Background Ethanol self-administration has been shown to increase dopamine in the nucleus accumbens; however, dopamine levels in the accumbal subregions (core, shell, and core-shell border) have not yet been measured separately in this paradigm. The present study was designed to determine if dopamine responses during operant ethanol self-administration are similar in the core, core-shell border and shell, particularly during transfer from the home cage to the operant chamber and during consumption of the drinking solution. Methods Six groups of male Long-Evans rats were trained to lever-press for either 10% sucrose (10S) or 10% sucrose + 10% ethanol (10S10E) (with a guide cannula above the core, core-shell border, or shell of the accumbens). On experiment day, five-min microdialysis samples were collected from the core, core-shell border, or shell before, during, and after drinking. Dopamine and ethanol concentrations were analyzed in these samples. Results A significant increase in dopamine occurred during transfer of the rats from the home-cage into the operant chamber in all six groups, with those trained to drink 10S10E exhibiting a significantly higher increase than those trained to drink 10S in the core and shell. No significant increases were observed during drinking of either solution in the core or shell. A significant increase in dopamine was observed during consumption of ethanol in the core-shell border. Conclusions We conclude that dopamine responses to operant ethanol self-administration are subregion specific. After operant training, accumbal dopamine responses in the core and shell occur when cues that predict ethanol availability are presented and not when the reinforcer is consumed. However, core-shell border dopamine responses occur at the time of the cue and consumption of the reinforcer.

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Background and Purpose Intracerebral hemorrhage (ICH) has high morbidity and hematoma enlargement (HE) causes worse outcome. Thrombelastography (TEG™) measures the dynamics of clot formation and dissolution, and might be useful for assessing bleeding risk. We used TEG™ to detect changes in clotting in patients with and without HE after ICH. Methods This prospective study included 64 patients with spontaneous ICH admitted from 2009 to 2013. TEG™ was performed within 6 hours of symptom onset and after 36 hours. Brain imaging was obtained at baseline and 36 ± 12 hours, and HE defined as total volume increase > 6cc or >33%. TEG™ was also obtained from 57 controls. Results Compared to controls, ICH patients demonstrated faster and stronger clot formation; shorter R and delta (p<0.0001) at baseline; and higher MA and G (p < 0.0001) at 36 hours. 11 patients had HE. After controlling for potential confounders, baseline K and delta were longer in HE + compared to HE − patients, indicating that HE+ patients had slower clot formation (p<0.05). TEG™ was not different between HE + and HE − patients at 36 hours. Conclusions TEG™ may detect important coagulation changes in patients with ICH. Clotting may be faster and stronger in immediate response to ICH and a less robust response may be associated with HE. These findings deserve further investigation.

Background Thromboelastography (TEG) measures the dynamics of coagulation. There are limited data about TEG in acute ischemic stroke other than a single study from 1974 suggesting that acute ischemic stroke patients are hypercoagulable. There have been no studies of TEG in the thrombolytic era despite its potential usefulness as a measure of clot lysis. This study was designed to provide initial TEG data in stroke patients before and after tissue plasminogen activator (tPA) therapy, and to provide the necessary preliminary data for further study of TEG’s ability to identify clot subtype and predict response to tPA therapy. Methods All acute ischemic stroke patients presenting between 11/2009 and 2/2011 eligible for tPA therapy were screened and 56 enrolled. Blood was drawn before (52 patients) and 10 minutes after tPA bolus (30 patients). Demographics, vitals, labs, 24hr National Institutes of Health Stroke Scale (NIHSS) and computed tomography (CT) scan results were collected. Patients were compared to normal controls. Results Acute ischemic stroke patients had shorter R (4.8±1.5 vs 6.0 ±1.7 min, p =0.0004), greater a-Angle (65.0±7.6 vs 61.5 ± 5.9°, p =0.01), and shorter K (1.7 ±0.7 vs 2.1 ±0.7 min, p =0.002) indicating faster clotting. Additionally, a subset formed clots with stronger platelet-fibrin matrices. Treatment with tPA resulted in reduction in all indices of clot strength (LY30=0(0–0.4) vs 94.4 (15.2–95.3) p<0.0001), however there was considerable variability in response. Conclusions TEG demonstrates that many acute ischemic stroke patients are hypercoaguable. TEG values reflect variable clot subtype and response to tPA. Further study based on these data will determine if TEG is useful for measuring the dynamic aspects of clot formation and monitoring lytic therapy.