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PubMed2005

Prefrontal serotonin depletion affects reversal learning but not attentional set shifting.

Recently, we have shown that serotonin (5-HT) depletion from the prefrontal cortex (PFC) of the marmoset monkey impairs performance on a serial discrimination reversal (SDR) task, resulting in perseverative responding to the previously correct stimulus (Clarke et al., 2004). This pattern of impairment is just one example of inflexible responding seen after damage to the PFC, with performance on the SDR task being dependent on the integrity of the orbitofrontal cortex. However, the contribution of 5-HT to other forms of flexible responding, such as attentional set shifting, an ability dependent on lateral PFC (Dias et al., 1996a), is unknown. The present study addresses this issue by examining the effects of 5,7-dihydroxytryptamine-induced PFC 5-HT depletions on the ability to shift attention between two perceptual dimensions of a compound visual stimulus (extradimensional shift). Monkeys with selective PFC 5-HT lesions, despite being impaired in their ability to reverse a stimulus-reward association, were unimpaired in their ability to make an extradimensional shift when compared with sham-operated controls. These findings suggest that 5-HT is critical for flexible responding at the level of changing stimulus-reward contingencies but is not essential for the higher-order shifting of attentional set. Thus, psychological functions dependent on different loci within the PFC are differentially sensitive to serotonergic modulation, a finding of relevance to our understanding of cognitive inflexibility apparent in disorders such as obsessive-compulsive disorder and schizophrenia.

5,7-Dihydroxytryptamine↗
PubMed1994

Ovarian steroid deprivation results in a reversible learning impairment and compromised cholinergic function in female Sprague-Dawley rats.

We hypothesized that estradiol (E2) serves as a neurotrophomodulatory substance for basal forebrain cholinergic neurons thought to be involved in learning and memory. Learning/memory was assessed using the two-way active avoidance paradigm and the Morris water task. Female Sprague-Dawley rats were either ovariectomized (OVX) or OVX for 3 weeks, followed by s.c. implantation of a Silastic pellet containing 17-beta E2 (E2 pellet), resulting in a replacement of E2 to physiological levels. Ovary-intact (INTACT) animals served as our positive control. Active avoidance behavior and choline acetyltransferase (ChAT) activity in the frontal cortex and hippocampus were assessed at 5 and 28 weeks postovariectomy while performance on the Morris water task and high-affinity choline uptake (HACU) were measured only at the 5-week time point. At the 5-week time point, E2 replacement caused a significant elevation in the level of active avoidance performance relative to OVX animals. At the 28-week time point, OVX animals demonstrated a significantly lower number of avoidances relative to controls (61%) whereas E2-pellet animals not only demonstrated superior performance relative to OVX animals but also showed an accelerated rate of learning. Morris water task performance, on the other hand, was not significantly affected by estrogenic milieu despite a trend towards better performance in the E2-pellet group. Neurochemical analyses revealed that 5 weeks of ovariectomy was sufficient to reduce HACU in both the frontal cortex and hippocampus by 24 and 34%, respectively, while E2 replacement was successful in elevating HACU relative to OVX animals in both regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗