Scopolamine-induced impairment in concurrent fixed-interval responding in a radial maze task.

The present study investigated the effects of scopolamine hydrobromide (SCOP: 0.06-1.0 mg/kg IP) and its quartenary analogue, scopolamine methylbromide (SCOPMB), on performance in a radial arm maze foraging task, to dissociate general drug-induced alterations of motor performance from measurement of impairments on more complex behaviors involving timing and memory. In this paradigm. rats are trained to free run a radial maze under an eight-alternative concurrent fixed-interval (FI) schedule of food reinforcement. The eight FIs (55 to 759 s) were assigned randomly to the arms of the maze, with a different pattern for each animal. SCOP produced dose-dependent degradation in response patterning and response rates in the concurrent FI schedules without significantly affecting the rates of arm entries or arm traversal latencies. The peripheral cholinergic antagonist, SCOPMB, generally produced small to moderate depressions in all measures with the exception of patterning of arm entries and pellets earned, but there were no clear dose-response relationships evident in the data. These results are consistent with the notion that central cholinergic mechanisms are involved in the mediation of complex conditioned behaviors.

Scopolamine impairs spatial working memory in the radial maze: an analysis by error type and arm choice.

The effects of scopolamine hydrobromide on performance in uninterrupted and delayed radial maze trials were studied in the rat. In addition to defining errors as incorrect arm entries, errors were defined by incorrect nose pokes in a food trough and were summed across the number of correct choices remaining. The average time elapsed from arm entry to nose poke was also calculated as a new measure of motivation and mobility. Working memory errors increased significantly following scopolamine injection in the uninterrupted trials and occurred significantly more often before the last correct choice. Errors in nonbaited arms during the last portion of a 3-h delay task increased significantly following scopolamine injection both before and after the first portion of the task and occurred more often before the last correct choice. However, nonbaited errors occurred more readily and at lower doses when scopolamine was injected 20 min before the onset of the task than when scopolamine was injected immediately after the completion of the first portion of the task. These data indicate that scopolamine affects current working memory and specifically affects acquisition more than consolidation of working memory.

Evidence for endorphin-mediated cross-tolerance between chronic stress and the behavioral effects of ionizing radiation.

C57BL/6J mice exhibit a naloxone-reversible locomotor hyperactivity after exposure to ionizing radiation. These data implicate endogenous opiates in this radiogenic behavioral change. Similarly, endorphins mediate analgesia produced by chronic stress (e.g., foot shock or restraint) and levels of plasma Beta-endorphin are elevated following exposure to acute stress. Therefore, the present study sought to determine if behavioral cross-tolerance could be obtained between endorphin-producing stressors and radiation exposure. Repeated pretreatment with foot shock or restraint subsequently inhibited the locomotor-activating effects of radiation. These data are consistent with the hypothesis that cross-tolerance developed between the effects of stress-induced endogenous opiate release and the radiation-induced release of endorphins.

Specific hormonal and neurochemical responses to different stressors.

The neuroendocrine and neurochemical responses of rats to 5 min of cold exposure versus 5 min of forced immobilization were determined and compared. We found that plasma hormones and brain neurochemical systems responded differently to the two different stressors. Plasma prolactin levels were elevated over 10-fold in the immolilized group, while rising only 2-fold in the cold stress group. Levels of corticosterone were significantly increased and growth hormone levels were decreased in both stressed groups as compared to controls. Levels of cyclic GMP were markedly elevated in 11 brain regions following cold exposure. Surprisingly, no elevation of cyclic GMP was found after forced immobilization. Cyclic AMP, norepinephrine, and dopamine levels throughout the 17 regions of brain examined showed no significant response to 5 min of either stressor. Lesions of the ventral medial tegmental area did not affect the cyclic GMP or neuroendocrine responses to cold stress. Lesion of the nucleus locus ceruleus did not affect the cyclic GMP response but significantly reduced growth hormone levels in the cold-stressed rats.

Effects of lesions of the ventral medial tegmentum on locomotor activity, biogenic amines and responses to amphetamine in rats.

Rats subjected to electrolytic lesions of the ventral medial tegmentum (VMT) showed long-lasting increased locomotor activity in the open field compared to sham-operated controls. In addition to severe depletion of mesolimbic dopamine, the lesions also caused significant depletions of striatal dopamine, mesolimbic and striatal norepinephrine and striatal and hippocampal serotonin. Administration of d-amphetamine sulfate produced similar dose-response functions for locomotor activity in both VMT-lesioned and sham-operated rats despite the extensive depletion of dopamine in the VMT-lesioned rats. These results suggest that the mesolimbic dopamine pathway is not the sole substrate for amphetamine-stimulated locomotor activity. Electrolytic lesions of the VMT interrupt several neurotransmitter pathways which may produce complex and antagonistic effects on behavior.