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Prenatal stress induces increased striatal dopamine transporter binding in adult nonhuman primates.

ABSTRACT: BACKGROUND:To determine the effects in adult offspring of maternal exposure to stress and alcohol during pregnancy, we imaged striatal and midbrain dopamine transporter (DAT) binding by positron emission tomography in rhesus monkeys (Macaca mulatta). We also evaluated the relationship between DAT binding and behavioral responses previously found to relate to dopamine D2 receptor density (responsivity to tactile stimuli, performance on a learning task, and behavior during a learning task). METHODS:Subjects were adult offspring derived from a 2 × 2 experiment in which pregnant monkeys were randomly assigned to control, daily mild stress exposure (acoustic startle), voluntary consumption of moderate-level alcohol, or both daily stress and alcohol. Adult offspring (n = 38) were imaged by positron emission tomography with the DAT ligand [(18)F]2?-carbomethoxy-3?-(4-chlorophenyl)-8-(2-fluoroethyl)-nortropane ([(18)F]FECNT). RESULTS:Results showed that prenatal stress yielded an overall increase of 15% in [(18)F]FECNT binding in the striatum (p = .016), 17% greater binding in the putamen (p = .012), and 13% greater binding in the head of the caudate (p = .028) relative to animals not exposed to prenatal stress. Striatal [(18)F]FECNT binding correlated negatively with habituation to repeated tactile stimulation and positively with tactile responsivity. There were no significant effects of prenatal alcohol exposure on [(18)F]FECNT binding. CONCLUSIONS:Maternal exposure to mild daily stress during pregnancy yielded increases in striatal DAT availability that were apparent in adult offspring and were associated with behavioral characteristics reflecting tactile hyperresponsivity, a condition associated with problem behaviors in children.

SUBMITTER: Converse AK

PROVIDER: S-EPMC3775901 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Prenatal stress induces increased striatal dopamine transporter binding in adult nonhuman primates.

Converse Alexander K AK Moore Colleen F CF Moirano Jeffrey M JM Ahlers Elizabeth O EO Larson Julie A JA Engle Jonathan W JW Barnhart Todd E TE Murali Dhanabalan D Christian Bradley T BT DeJesus Onofre T OT Holden James E JE Nickles Robert J RJ Schneider Mary L ML

Biological psychiatry 20130529 7

<h4>Background</h4>To determine the effects in adult offspring of maternal exposure to stress and alcohol during pregnancy, we imaged striatal and midbrain dopamine transporter (DAT) binding by positron emission tomography in rhesus monkeys (Macaca mulatta). We also evaluated the relationship between DAT binding and behavioral responses previously found to relate to dopamine D2 receptor density (responsivity to tactile stimuli, performance on a learning task, and behavior during a learning task) ...[more]

PMID: 23726316

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Project description:Background/objectiveChanges in brain metabolism has been investigated thoroughly during unilateral cervical chronic vagal stimulation in epileptic or depressive patients. Bilateral stimulation of the abdominal vagus (aVNS) has received less attention despite the reduction in body weight and an altered feeding behavior in obese animals that could be clinically relevant in obese individuals. Our study aims to examine the changes in brain glucose metabolism (CMRglu) induced by aVNS in obese adult miniature pigs. Dopamine (DAT) and serotonin transporters (SERT) were also quantified to further understand the molecular origins of the alterations in brain metabolism.Subjects/methodsPairs of stimulating electrodes were implanted during laparoscopy on both abdominal vagal trunks in 20 obese adult's miniature pigs. Half of the animals were permanently stimulated while the remaining were sham stimulated. Two months after the onset of stimulation, dynamic 18FDG PET and 123I-ioflupane SPECT were performed. Food intake, resting energy expenditure and fat deposition were also assessed longitudinally.ResultsFood intake was halved and resting energy expenditure was increased by 60% in aVNS group compared to sham. The gain in body weight was also 38% less in aVNS group compared to sham. Brain metabolic connectivity increased between numerous structures including striatum, mid-brain, amygdala and hippocampus. On the contrary, increased CMRglu were restricted to the thalamus, the periaqueducal grey and the amygdala. DAT binding potential was decreased by about one third in the striatum while SERT was about doubled in the midbrain.ConclusionsOur findings demonstrated that aVNS reduced weight gain as a consequence of diminished daily food intake and increased resting energy expenditure. These changes were associated with enhanced connectivity between several brain areas. A lower striatal DAT together with a doubled mid-brain SERT were likely causative for these changes.

Dataset Information

Prenatal stress induces increased striatal dopamine transporter binding in adult nonhuman primates.

Publications

Prenatal stress induces increased striatal dopamine transporter binding in adult nonhuman primates.

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