Early life stress as a risk factor for substance use disorders: Clinical and neurobiological substrates
Background: Early Life Stress (ELS) can profoundly influence an individual′s genotype and phenotype. Effects of ELS can manifest in the short-term, late life and even in subsequent generations. ELS activate corticotrophin releasing factor (CRF); CRF influences drug seeking and addiction. The aim of...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2015-01-01
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| Series: | Indian Journal of Psychological Medicine |
| Subjects: | |
| Online Access: | http://www.ijpm.info/article.asp?issn=0253-7176;year=2015;volume=37;issue=1;spage=36;epage=41;aulast=Varghese |
| _version_ | 1818740252072738816 |
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| author | Sajoy Purathumuriyil Varghese Janitza L Montalvo-Ortiz John G Csernansky Rodney I Eiger Amy A Herrold Maju Mathew Koola Hongxin Dong |
| author_facet | Sajoy Purathumuriyil Varghese Janitza L Montalvo-Ortiz John G Csernansky Rodney I Eiger Amy A Herrold Maju Mathew Koola Hongxin Dong |
| author_sort | Sajoy Purathumuriyil Varghese |
| collection | DOAJ |
| description | Background: Early Life Stress (ELS) can profoundly influence an individual′s genotype and phenotype. Effects of ELS can manifest in the short-term, late life and even in subsequent generations. ELS activate corticotrophin releasing factor (CRF); CRF influences drug seeking and addiction. The aim of this study was to examine the effects of endogenous elevated levels of CRF on addiction. Materials and Methods: Inducible forebrain over-expression of CRF mice (tetop-CRH x CaMKII-tTA) was used for this study. Morphine (10 mg/kg) was administered every other day for 10 days or with increasing doses of morphine: 20, 40, 60, 80, 100, and 100 mg/kg. The behavioral trials including morphine sensitization, Somatic Opiate Withdrawal Symptoms (SOWS) were conducted in a single, open field, activity. After behavioral trial, animals were perfused for immunohistochemistry analysis. Results: CRF-over expressed (CRF-OE) mice showed increase in morphine sensitization and withdrawal symptoms after morphine administration compared to wild type (WT) mice. The two-way ANOVA in the morphine sensitization study showed a significant effect of treatment (P<0.05) and genotype for distance traveled (P<0.01). In the SOWS study, opiate withdrawal symptoms such as rearings, circling behavior, grooming, and jump in CRF-OE were amplified in parallel to WT mice. In the immunohistochemistry study, pro-dynorphine (PDYN) expression was increased after morphine administration in both amygdala and nucleus accumbens (NAcc). Conclusions: CRF-OE in the forebrain increases the sensitization and withdrawal symptoms in morphine treated mice. On exposure to morphine, in CRF-OE mice the PDYN protein expression was increased as compared to WT mice in the amygdala and NAcc. |
| first_indexed | 2024-12-18T01:37:46Z |
| format | Article |
| id | doaj.art-91890f06cde84a3dac21b5cdce8b01ea |
| institution | Directory Open Access Journal |
| issn | 0253-7176 |
| language | English |
| last_indexed | 2024-12-18T01:37:46Z |
| publishDate | 2015-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Indian Journal of Psychological Medicine |
| spelling | doaj.art-91890f06cde84a3dac21b5cdce8b01ea2022-12-21T21:25:25ZengSAGE PublishingIndian Journal of Psychological Medicine0253-71762015-01-01371364110.4103/0253-7176.150816Early life stress as a risk factor for substance use disorders: Clinical and neurobiological substratesSajoy Purathumuriyil VargheseJanitza L Montalvo-OrtizJohn G CsernanskyRodney I EigerAmy A HerroldMaju Mathew KoolaHongxin DongBackground: Early Life Stress (ELS) can profoundly influence an individual′s genotype and phenotype. Effects of ELS can manifest in the short-term, late life and even in subsequent generations. ELS activate corticotrophin releasing factor (CRF); CRF influences drug seeking and addiction. The aim of this study was to examine the effects of endogenous elevated levels of CRF on addiction. Materials and Methods: Inducible forebrain over-expression of CRF mice (tetop-CRH x CaMKII-tTA) was used for this study. Morphine (10 mg/kg) was administered every other day for 10 days or with increasing doses of morphine: 20, 40, 60, 80, 100, and 100 mg/kg. The behavioral trials including morphine sensitization, Somatic Opiate Withdrawal Symptoms (SOWS) were conducted in a single, open field, activity. After behavioral trial, animals were perfused for immunohistochemistry analysis. Results: CRF-over expressed (CRF-OE) mice showed increase in morphine sensitization and withdrawal symptoms after morphine administration compared to wild type (WT) mice. The two-way ANOVA in the morphine sensitization study showed a significant effect of treatment (P<0.05) and genotype for distance traveled (P<0.01). In the SOWS study, opiate withdrawal symptoms such as rearings, circling behavior, grooming, and jump in CRF-OE were amplified in parallel to WT mice. In the immunohistochemistry study, pro-dynorphine (PDYN) expression was increased after morphine administration in both amygdala and nucleus accumbens (NAcc). Conclusions: CRF-OE in the forebrain increases the sensitization and withdrawal symptoms in morphine treated mice. On exposure to morphine, in CRF-OE mice the PDYN protein expression was increased as compared to WT mice in the amygdala and NAcc.http://www.ijpm.info/article.asp?issn=0253-7176;year=2015;volume=37;issue=1;spage=36;epage=41;aulast=VargheseCorticotrophin-releasing factorearly life stressopioid use disordersubstance use disordersmorphine |
| spellingShingle | Sajoy Purathumuriyil Varghese Janitza L Montalvo-Ortiz John G Csernansky Rodney I Eiger Amy A Herrold Maju Mathew Koola Hongxin Dong Early life stress as a risk factor for substance use disorders: Clinical and neurobiological substrates Indian Journal of Psychological Medicine Corticotrophin-releasing factor early life stress opioid use disorder substance use disorders morphine |
| title | Early life stress as a risk factor for substance use disorders: Clinical and neurobiological substrates |
| title_full | Early life stress as a risk factor for substance use disorders: Clinical and neurobiological substrates |
| title_fullStr | Early life stress as a risk factor for substance use disorders: Clinical and neurobiological substrates |
| title_full_unstemmed | Early life stress as a risk factor for substance use disorders: Clinical and neurobiological substrates |
| title_short | Early life stress as a risk factor for substance use disorders: Clinical and neurobiological substrates |
| title_sort | early life stress as a risk factor for substance use disorders clinical and neurobiological substrates |
| topic | Corticotrophin-releasing factor early life stress opioid use disorder substance use disorders morphine |
| url | http://www.ijpm.info/article.asp?issn=0253-7176;year=2015;volume=37;issue=1;spage=36;epage=41;aulast=Varghese |
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