Brain 5-HT receptor system in the stressed infant rat: implications for vulnerability to substance abuse.
Clinical and epidemiological studies have found an association between aversive experiences early in life and an increased risk for depression, anxiety and substance abuse. In order to elucidate the mechanisms by which adverse life events are translated into behavioral and psychological abnormalities, we used a rat model to study the impact of chronic injection and 24 h maternal deprivation on the developing rat brain. Specifically, we investigated the regulation of molecules related to the 5-HT (5-HT) system and studied the effect of desipramine administration on animals that were maternally deprived (DEP) on day 13 of life compared with non-deprived animals. We found that maternal deprivation caused an enhanced corticosterone response to an acute stress. Maternally deprived animals also showed a decrease in corticosteroid receptors and an increase in 5-HT 1A and 1B receptors restricted to the CA1 region of the hippocampus. Desipramine prevented the maternal deprivation induced up-regulation of the 5-HT 1B receptor and the enhanced adrenocortical response observed in these animals. Interestingly, non-deprived animals receiving chronic injections showed a decrease in hippocampal 5-HT1B receptor mRNA. At 80 days of age, a group of animals that were treated as infants were given the option of drinking from two identical water bottles, one bottle contained tap water, while the second contained ethanol at increasing concentrations. Animals that received chronic injections during the newborn period consumed more alcohol than those that were not injected. On the other hand, maternal deprivation did not have an impact on alcohol consumption. Alcohol preference has implications to the organism since studies of drug self-administration in laboratory animals have shown that ethanol ingestion is positively related to the use of other drugs, principally opioids and psychostimulants. Our findings suggest that the quality and/or chronicity of early life stressors can influence the neurobiological substrates that may trigger and/or predispose individuals to substance abuse in adulthood.
Vázquez
Delia M
DM
Department of Pediatrics, University of Michigan, Medical Science Research Building, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0646, USA. dmvazq@umich.edu
Eskandari
Ramin
R
Zimmer
Carrie A
CA
Levine
Seymour
S
López
Juan F
JF
D000302:Adrenal Cortex / Q000502:physiology; D000428:Alcohol Drinking / Q000523:psychology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D001345:Autoradiography; D001923:Brain Chemistry / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D002908:Chronic Disease; D003720:Densitometry; D003891:Desipramine / Q000627:therapeutic use; D005260:Female; D017403:In Situ Hybridization; D008297:Male; D008426:Maternal Deprivation; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism; D015347:RNA Probes; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D050486:Serotonin Plasma Membrane Transport Proteins; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000378:metabolism* / Q000517:prevention & control
D000929:Antidepressive Agents, Tricyclic; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D015347:RNA Probes; D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D003891:Desipramine