Adult hippocampal neurogenesis has been implicated in cognitive and emotional processes, and in response to antidepressant treatment. However, little is known about how the adult stem cell lineage contributes to hippocampal structure and function and how this process is modulated by the animal’s experience. Here we perform an indelible lineage analysis and report that neural stem cells can produce expanding and persisting populations of not only neurons, but also stem cells in the adult hippocampus. Furthermore, the ratio of stem cells to neurons depends on experiences of the animal or the location of the stem cell. Surprisingly, social isolation facilitated accumulation of stem cells, but not neurons. These results show that neural stem cells accumulate in the adult hippocampus, and that the stem cell-lineage relationship is under control of anatomic and experiential niches. Our findings suggest that, in the hippocampus, fate specification may act as a form of cellular plasticity for adapting to environmental changes.

Objectives-We used a Positron Emission Tomography (PET) paradigm with the D 2/3 radiotracer [ 11 C]raclopride and an alcohol challenge to examine the magnitude of alcohol induced dopamine release and compare it between young men and women.Methods-Twenty-one non-alcohol dependent young social drinkers completed two PET scans on separate days following ingestion of a juice mix containing either ethanol (0.75 mg/kg body water) or trace ethanol only.The extent of dopamine released after alcohol was estimated by the percent difference in [ 11 C]raclopride binding potential (ΔBP ND ) between days.Results-Alcohol administration significantly displaced [ 11 C]raclopride in all striatal subregions indicating dopamine release, with the largest effect observed in the ventral striatum. Linear mixed model analysis across all striatal subregions of regional ΔBP ND with region of interest as repeated measure showed a highly significant effect of sex (p < 0.001). Ventrostriatal dopamine release in men, but not in women, showed a significant positive correlation to alcohol-induced measures of subjective activation. Furthermore, we found a significant negative correlation between the frequency of maximum alcohol consumption per 24 hours and ventrostriatal ΔBP ND (r=0.739, p=0.009) in men.Conclusions-This study provides definitive evidence that oral alcohol induces dopamine release in non-alcoholic human subjects, and shows sex differences in the magnitude of this effect. The ability of alcohol to stimulate dopamine release may contribute to its rewarding effects and, thereby, to its abuse liability in humans. Our report further suggests several biological mechanisms that may mediate the difference in vulnerability for alcoholism between men and women.

Background Alterations in dopamine D2/D3 receptor binding have been reported in schizophrenia, and a meta-analysis of imaging studies has shown a modest elevation in striatum. Newer radioligands now allow the assessment of these receptors in extrastriatal regions. We used PET with [18F]fallypride to evaluate D2/D3 receptors in both striatal and extrastriatal regions in schizophrenia. Methods Twenty-one patients with schizophrenia and 22 matched healthy controls were scanned with an HR+ camera. Two-tissue compartment modeling (2TCM) and the reference tissue method gave binding potentials BPND, BPP, and BPF which were compared between groups in five striatal and 8 extrastriatal regions. Several regional volumes were lower in the patient group, and PET data were corrected for partial volume effects. Results BP values differed in three regions between groups. BPND values from 2TCM in patients and controls respectively were 28.7 ± 6.8 and 25.3 ± 4.3 in post-commissural caudate, 2.9 ± 0.7 and 2.6 ± 0.4 in thalamus, and 1.8 ± 0.5 and 2.1 ± 0.7 in uncus. Loss of D2/D3 receptors with age was found in striatal and extrastriatal regions and was greater in neocortex. Conclusions Our study found selective alterations in D2/D3 receptors in striatal and extrastriatal regions, consistent with some but not all previously published reports. As previously shown for the striatum, a more sensitive imaging approach for studying the role of dopamine in the pathophysiology of schizophrenia might be assessment of neurotransmitter levels rather than D2/D3 receptor levels in extrastriatal regions.