Possible Äccelerated Striatal Aging" Induced by 56 Fe Heavy-Particle Irradiation: Implications for Manned Space Flights

Abstract

The present experiments were carried out to determine the effects of energy deposition from energetic iron (56Fe particles, an important component of cosmic rays) on motor behavioral performance and to determine if the observed deficits were caused by alterations in the neostriatum (an important motor control area). Neostriatal function was assessed with two correlated parameters, i.e., motor behavioral performance (wire suspension task), and oxotremorine-enhanced K(+)-evoked release of dopamine from perifused striatal slices. Rats were exposed to one of several doses of 56Fe-particle irradiation (0.10-1.0 Gy) and tested on a wire suspension task at 3-180 days postirradiation. Results indicated that profound decrements occurred in both of these indices. The effects on K(+)-evoked release of dopamine were evident for as long as 180 days after irradiation, and a subsequent experiment indicated that these effects appeared as early as 12 h postirradiation. Since similar findings have been observed in aged rats, the results are discussed in terms of these particles producing a possible accelerated striatal aging effect.

Amphetamine-induced taste aversion learning in young and old F-344 rats following exposure to 56Fe particles

“…Because amphetamine is a dopamine agonist, the development of an amphetamineinduced CTA requires an intact dopamine system (Rabin et al 1998), and the disruption of dopaminergic function by heavy particle irradiation interferes with behaviors that are dependent upon the integrity of that system. Overall, the deficits observed following exposure to HZE particles are similar to those that are observed in old animals, which suggest that exposure to low doses of HZE particles produces "accelerated aging" (Joseph et al 1992(Joseph et al , 1993.…”

“…Specifically, the 3-day interval was selected because previous experiments on the effects of exposure to HZE particles (Joseph et al 1992) had shown a maximal reduction in dopamine release 3 days following exposure to 56 Fe particles. In addition, research on the disruption of amphetamine-induced CTA learning has utilized a single injection of amphetamine on the conditioning day and a 24-h interval between conditioning and test days.…”

“…Because both the aging process (Baker et al 1997;Friedman and Gerhardt 1992;Shukitt-Hale et al 2002) and exposure to HZE particles disrupt dopaminergic function (Joseph et al 1992(Joseph et al , 1993, it is possible that there may be an interaction between age and irradiation, such that exposing older rats to lower doses of 56 Fe particles will interfere with the acquisition of an amphetamine-induced CTA. Previous studies have shown that exposing rats to doses of 56 Fe particles which do not affect operant performance in young rats (≈2 months of age) produces deficits in performance in older animals (Rabin et al , 2005.…”

“…Exposing rats to heavy particles (HZE particles), a ground-based model for exposure to cosmic rays, disrupts the functioning of the dopaminergic system (Joseph et al 1992(Joseph et al , 1993 and the behaviors that are dependent upon the integrity of that system (Joseph et al 1992;Rabin et al 1998Rabin et al , 2003Shukitt-Hale et al 2000. In addition to the effects of irradiation on cognitive performance, exposure to 56 Fe particles disrupts the acquisition of an amphetamine-induced CTA, but does not affect the acquisition of a CTA produced by administration of lithium chloride (Rabin et al 1998.…”

Interaction between age of irradiation and age of testing in the disruption of operant performance using a ground-based model for exposure to cosmic rays

“…These deficits are similar to those that are characteristic of the aged organism, including deficits in signal transduction (Joseph et al 1992(Joseph et al , 1993Casadesus et al 2005;Denisova et al 2002), amphetamine-induced taste aversion learning (Rabin et al 1998), spatial learning and memory using the Morris water maze Carey et al 2007), and operant responding . Previous research has shown that rats exposed to 56 Fe particles at a young age (2 months) show a progressive deterioration in operant responding on an ascending fixed-ratio (FR) reinforcement schedule as a function of time following irradiation such that doses of particles that did not affect the responding of younger animals did affect their responding as they aged (Rabin et al , 2005a.…”