Cardiac 123I-MIBG normal uptake values are population-specific: Results from a cohort of controls over 60 years of age.

PURPOSE: Cardiac 123I-MIBG image interpretation is affected by population differences and technical factors. We recruited older adults without cognitive decline and compared their cardiac MIBG uptake with results from the literature. METHODS: Phantom calibration confirmed that cardiac uptake results from Japan could be applied to our center. We recruited 31 controls, 17 individuals with dementia with Lewy bodies (DLB) and 15 with Alzheimer's disease (AD). Images were acquired 20 minutes and four hours after injection using Siemens cameras with medium-energy low-penetration (MELP) collimators. Local normal heart-to-mediastinum (HMR) ratios were compared to Japanese results. RESULTS: Siemens gamma cameras with MELP collimators should give HMRs very close to the calibrated values used in Japan. However, our cut-offs with controls were lower at 2.07 for early and 1.86 for delayed images. Applying our lower cut-off to the dementia patients may increase the specificity of cardiac MIBG imaging for DLB diagnosis in a UK population without reducing sensitivity. CONCLUSIONS: Our local HMR cut-off values are lower than in Japan, higher than in a large US study but similar to those found in another UK center. UK centers using other cameras and collimators may need to use different cut-offs to apply our results.

First passage time distribution of multiple impatient particles with reversible binding.

Consider N independently diffusing particles that reversibly bind to a target. We study a problem recently introduced by Grebenkov of finding the first passage time (FPT) for K of the N particles to be simultaneously bound to the target. Since binding is reversible, bound particles may unbind before the requisite K particles bind to the target. This so-called "impatience" leads to a delicate temporal coupling between particles. Recent work found the mean of this FPT in the case that N = K = 2 in a one-dimensional spatial domain. In this paper, we approximate the full distribution of the FPT for any N ≥ K ≥ 1 in a broad class of domains in any space dimension. We prove that our approximation (i) is exact in the limit that the target and/or binding rate is small and (ii) is an upper bound in any parameter regime. Our approximation is analytically tractable and we give explicit formulas for its mean and distribution. These results reveal that the FPT can depend sensitively and nonlinearly on both K and N. The analysis is accompanied by detailed numerical simulations.

Magnesium-maintained self-administration responding in cocaine-trained rats.

Magnesium chloride (MgCl2) produces behavioral effects similar to those of psychomotor stimulants in a variety of behavioral situations. Because MgCl2 appears to have stimulant properties, the ability of MgCl2 to maintain responding in a rat self-administration paradigm was examined in seven experiments under different access and schedule conditions in cocaine-trained rats. These varied from the availability of MgCl2 for a single day's test session subsequent to 1 h availability of cocaine, to the availability of MgCl2 for 10 or 20 days after cocaine availability was totally discontinued. Fixed ratio 1, fixed ratio 5, and progressive ratio 1, 2 and 3 schedules of drug delivery were used. The results demonstrate that MgCl2 may substitute for self-administered cocaine because it maintained responding; it did so dose dependently to maintain a constant level of MgCl2 intake; and it did so over a 10-day period of time both with and without access to cocaine on test days. Responding maintained by MgCl2 when cocaine was no longer available was similar under fixed ratio 1 and 5 schedule conditions. The progressive ratio breakpoints for MgCl2 were significantly higher than those for saline, but significantly lower than those for cocaine. These data indicate that MgCl2 has some reinforcing efficacy in cocaine-trained rats, particularly under fixed ratio 1 and 5 schedules, but has a low abuse potential compared to cocaine.

Postconditioning effects of magnesium on cocaine conditioned place preference in mice.

Magnesium chloride (MgCl2) has recently been shown to have stimulant-like properties. Because stimulants are known to induce conditioned place preference (CPP), the CPP procedure was used to test the hypothesis that cocaine and MgCl2 share similar stimulus properties. This would be shown if cocaine-induced CPP could be enhanced in a postconditioning preference test by MgCl2 and other stimulants. Mice were conditioned with 5.0 mg/kg cocaine to the nonpreferred end of a three-compartment straight shuttle box. All groups showed significant shifts in preference from the preconditioning test to the postconditioning test. There were no changes in place preference over test days in mice that were injected only with saline and therefore not conditioned. When animals were given acute injections of either saline, 5.0 mg/kg cocaine, 1.0 mg/kg amphetamine, 30 mg/kg MgCl2, 10 mg/kg pentobarbital, or 0.25 mg/kg haloperidol following conditioning with cocaine, amphetamine and MgCl2 elevated the conditioned cocaine effect, and pentobarbital and haloperidol decreased the conditioned cocaine effect compared to saline. In addition, there was a dose-dependent influence of MgCl2, with 30 mg/kg producing the maximum effect on the conditioned cocaine effect.

Magnesium-induced conditioned place preference in mice.

A conditioned place preference procedure was used in mice to test the hypothesis that magnesium possesses reinforcing properties. Mice were conditioned to the nonpreferred end of a three-compartment straight shuttle box with MgCl2 injections alternating with saline injections on the preferred end. Dose of MgCl2 was varied (0, 15, 30, 125 mg/kg) as well as number of conditioning trials (8 or 16). On the day after the first postconditioning test, animals were given acute injections of 5 mg/kg cocaine, or other test drug, to determine if the conditioned effect on behavior would be potentiated, maintained or blocked by these test drugs. Results demonstrated that 15 mg/kg MgCl2 induced the greatest amount of conditioning and that increasing the number of MgCl2/place pairings did not enhance the amount of conditioning, but rather, it decreased it. Amphetamine potentiated MgCl2-induced place preference; cocaine and pentobarbital maintained it; and haloperidol blocked it. These data indicate that MgCl2 has some primary reinforcing properties in mice and that MgCl2 shares stimulus properties with other stimulants and reinforcing substances.

Failure of magnesium to maintain self-administration in cocaine-naive rats.

Previous research has shown that magnesium interacts with cocaine in such a way that it potentiates its action in a variety of behavioral situations. More recently, it has been demonstrated that magnesium will dose dependently substitute for cocaine self-administration and reduce the intake of cocaine. It is of considerable interest to determine if magnesium would be self-administered in cocaine-naive animals. The results of two experiments demonstrate that magnesium is not self-administered by cocaine-naive rats since although responding for magnesium chloride is above hypertonic saline control levels on day 1 of access, this responding is not maintained on subsequent days, does not occur in a regularly spaced pattern over time, and is not inversely related to dose. Taken together these data indicate that magnesium is a substitute for cocaine that has low abuse potential.

Acute and multiple injection effects of magnesium on responding maintained by cocaine, extinction from cocaine, glucose + saccharin, and food.

In a variety of behavioral experiments, magnesium has effects that are similar to cocaine and other psychomotor stimulants. Of particular relevance to the present experiments is the recent finding that magnesium maintains responding in cocaine-trained rats. It would be expected, therefore, that injections of magnesium would alter the rate of responding maintained by self-administered cocaine in rats. Five experiments examined the specificity and selectivity of this interaction. Acute and multiple injections of MgCl2 (15-250 mg/kg) produced dose-dependent reductions in responding maintained by cocaine (0.1-2 mg/kg/infusion). Testing for acute injection effects occurred following injections, while testing for multiple injection effects occurred prior to daily injections. Doses of 30 and 125 mg/kg MgCl2 reduced responding maintained by doses of cocaine that were below the training dose of 0.75 mg/kg/infusion. MgCl2 in a dose of 250 mg/kg markedly suppressed responding maintained by each dose of cocaine. A magnesium-deficient diet produced a dose-dependent increase in responding maintained by 0.1 mg/kg/infusion cocaine. In order to determine the specificity and selectively of these effects, acute and multiple injections of MgCl2 were examined on glucose + saccharin- and food-maintained responding. The acute effects of MgCl2 injections were specific because food-maintained responding was not affected, except by the highest dose of 250 mg/kg. This demonstrates that lever pressing was not nonspecifically reduced by 30 and 125 mg/kg MgCl2 during cocaine availability. However, the effects on cocaine-maintained responding were not selective for cocaine because glucose + saccharin-maintained responding and responding during extinction from cocaine were affected by MgCl2 in a manner similar to cocaine-maintained responding.(ABSTRACT TRUNCATED AT 250 WORDS)