Differential effects of antipsychotics on lateral bias and social attention in female rats.

RATIONALE: Prior research has demonstrated that individuals with schizophrenia may exhibit lateral biases in attention and deficits in social behavior. The use of a noninvasive animal model of attentional impairments in schizophrenia and antipsychotic drugs can help elucidate the biological underpinnings of attentional processes and facilitate the study of novel therapeutics. OBJECTIVES: The purpose of this study was to compare the effects of three antipsychotic drugs on measures of lateral bias and social attention in healthy, unoperated female rats. MATERIALS AND METHODS: Female Long-Evans rats selected for a preexisting lateral bias in attention, a right behavioral orientation preference (BOP), were administered clozapine, haloperidol, sulpiride, or vehicle. Lateral bias in attention was assessed by determining which forelimb rats removed a nuisance stimulus from first. Social attention was examined by comparing the latency to remove nuisance stimuli in the presence of a social (inaccessible female rat) versus non-social (blinking clock) distractor. RESULTS: All antipsychotic drugs eliminated right lateral bias in attention, while control animals retained their initial bias. Clozapine eliminated right lateral bias more rapidly than the other drugs. Animals receiving clozapine also selectively displayed increased attention to another rat. CONCLUSIONS: The results suggest that the antipsychotic medication clozapine rapidly alters attentional bias and uniquely influences attention to a social stimulus. The right BOP paradigm is a useful animal model for comparing antipsychotic drug effects on lateralized attentional bias and attention to social stimuli.

Antidepressive effects of the κ-opioid receptor agonist salvinorin A in a rat model of anhedonia.

Salvinorin A (SalvA), the hallucinogenic derivative of the plant Salvia divinorum, is a selective κ-opioid receptor agonist that may also have antidepressant properties. Chronic mild stress (CMS) was applied to male and female Long-Evans rats to model anhedonia common in depression. The progressive loss in preference for a sucrose solution over plain water, a measure of anhedonia, and locomotor activity were monitored for 7 weeks. Because antidepressant medications often modify reproductive functions, endocrine glands and hormone-sensitive tissues were assessed at necropsy after the conclusion of the behavioral protocol. Three weeks of CMS exposure led to a decrease in sucrose preference. CMS was continued for 3 additional weeks and animals were randomly assigned to treatment with 1 mg SalvA/kg body weight or to a vehicle control group. The results indicate that SalvA reversed anhedonia whereas control animals continued to show a suppressed preference for the sucrose solution. In addition, no change in sucrose preference was observed in nonstressed rats that were exposed to the same dosage of SalvA. The results indicate that SalvA is an effective antidepressant agent when administered chronically to rats showing symptoms of depression similar to those observed in humans.

Cognitive training-related changes in hippocampal activity associated with recollection in older adults.

Impairments in the ability to recollect specific details of personally experienced events are one of the main cognitive changes associated with aging. Cognitive training can improve older adults' recollection. However, little is currently known regarding the neural correlates of these training-related changes in recollection. Prior research suggests that the hippocampus plays a central role in supporting recollection in young and older adults, and that age-related changes in hippocampal function may lead to age-related changes in recollection. The present study investigated whether cognitive training-related increases in older adults' recollection are associated with changes in their hippocampal activity during memory retrieval. Older adults' hippocampal activity during retrieval was examined before and after they were trained to use semantic encoding strategies to intentionally encode words. Training-related changes in recollection were positively correlated with training-related changes in activity for old words in the hippocampus bilaterally. Positive correlations were also found between training-related changes in activity in prefrontal and left lateral temporal regions associated with self-initiated semantic strategy use during encoding and training-related changes in right hippocampal activity associated with recollection during retrieval. These results suggest that cognitive training-related improvements in older adults' recollection can be supported by changes in their hippocampal activity during retrieval. They also suggest that age differences in cognitive processes engaged during encoding are a significant contributor to age differences in recollection during retrieval.