In the laboratory rat and guinea pig, glucocorticoids (GCs), the adrenal steroids that are secreted during stress, can damage the hippocampus and exacerbate the hippocampal damage induced by various neurological insults. An open question is whether GCs have similar deleterious effects in the primate hippocampus. In fact, we showed that sustained and fatal stress was associated with preferential hippocampal damage in the vervet monkey; however, it was not possible to determine whether the excessive GC secretion that accompanied such stress was the damaging agent. The present study examines this possibility. Pellets of cortisol (the principal GC of primates) were stereotaxically implanted into hippocampi of 4 vervet monkeys; contralateral hippocampi were implanted with cholesterol pellets as a control. One year later at postmortem, preferential damage occurred in the cortisol-implanted side. In the cholesterol side, mild cell layer irregularity was noted in 2 of 4 cases. By contrast in the cortisol-exposed hippocampi, all cases had at least 2 of the following neuropathologic markers: cell layer irregularity, dendritic atrophy, soma shrinkage and condensation, or nuclear pyknosis. Damage was severe in some cases, and was restricted to the CA3/CA2 cellfield. This anatomical distribution of damage, and the cellular features of the damage agree with that observed in instances of GC-induced toxicity in the rodent hippocampus, and of stress-induced toxicity in the primate hippocampus. These observations suggest that sustained GC exposure (whether due to stress, Cushings syndrome or exogenous administration) might damage the human hippocampus.

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Negative slow potential change (contingent negative variation or CNV) in human cortex which develops in the foreperiod of a reaction-time experiment was studied as a function of motivational variables. When the warning signal indicated that a difficult-to-detect auditory stimulus would follow, CNV was greater than when an easily detected stimulus was signaled. Instructing Ss to press a key at the onset of the second stimulus resulted in development of larger anticipatory CNV than when no response was instructed. When muscular effort required to complete a response to the 2nd stimulus was varied, larger CNV accompanied greater effort. These findings extend those of other investigators and support the conclusion that CNV reflects cerebral mechanisms related to motivation.

The effects of the antineoplastic drugs vincristine, maytansine and cis-platinum were studied to determine the appropriateness of a behavioral and electrophysiological test battery for characterizing the neurotoxicity of such therapeutic compounds. Single- and repeated-dose studies in rats were performed initially, to establish doses for the subchronic neurobehavioral study. Measurements obtained in the subchronic study included body weight, rectal temperature, forelimb and hindlimb grip strengths; performance of a multisensory conditional avoidance response task and other behavioral tests; and a series of evoked responses (ventral caudal nerve action potential, brainstem auditory response and responses from other modalities). The drugs were injected intraperitoneally 5 days per week for 7 weeks. The rats were tested weekly during baseline, treatment and recovery phases. Each drug caused a different pattern of effects, but they all altered body weight, rectal temperature, peripheral nerve conduction velocity, the somatosensory evoked potential and undifferentiated motor activity. cis-Platinum was the most toxic, and maytansine was the least toxic. The results indicated that some elements of the test battery were useful for evaluating the neurotoxicity of anticancer drugs. However, other tests - notably, a test of negative geotaxis and the cortical auditory evoked response - were unreliable.