Individual differences in gene expression of vasopressin, D2 receptor, POMC and orexin: vulnerability to relapse to heroin-seeking in rats.
- Authors
- Zhou, Yan; Leri, Francesco; Cummins, Erin; Kreek, Mary Jeanne
- Year
- 2015
- Journal
- Physiology & behavior
- PMID
- 25446223
- DOI
- 10.1016/j.physbeh.2014.11.002
- PMCID
- PMC4275356
Individual vulnerability to stress-induced relapse during abstinence from chronic heroin exposure is a key feature of opiate addiction, with limited studies on this topic. Arginine vasopressin (AVP) and its V1b receptor, components of the brain stress responsive systems, play a role in heroin-seeking behavior triggered by foot shock (FS) stress in rats. In this study, we tested whether individual differences in the FS-induced heroin-seeking were associated with alterations of AVP and V1b, as well as other stress responsive systems, including pro-opiomelanocortin (POMC), orexin, plasma ACTH and corticosterone, as well as dopamine D2 receptor (D2) and plasma prolactin. Sprague-Dawley rats were subjected to 3-hour intravenous heroin self-administration (SA) and then tested in extinction, and FS-induced and heroin priming-induced reinstatements. The rats that self-administered heroin were divided into high and low reinstatement responders induced by FS (H-RI; L-RI). Over SA sessions, both the H-RI and L-RI displayed similar active lever responding, heroin infusion and total heroin intake. Compared to the L-RI, however, the H-RI showed greater active lever responses during stress-induced reinstatement, with higher AVP mRNA levels in medial/basolateral amygdala and lower D2 mRNA levels in caudate putamen. However, heroin priming resulted in similar reinstatement in both groups and produced similarly low POMC and high orexin mRNA levels in hypothalamus. Our results indicate that: 1) enhanced amygdalar AVP and reduced striatal D2 expression may be related to individual vulnerability to stress-induced reinstatement of heroin- seeking; and 2) heroin abstinence-associated alterations of hypothalamic orexin and POMC expression may be involved in drug priming-induced heroin-seeking.
Comparison of heroin self-administration (SA) behavioral responses. The panels show the mean (sem) actual self-infusions obtained (A, B) and the mean (sem) heroin total intake (mg/kg) (C, D) over the seven 3-h sessions of heroin SA (0.05 mg/kg/infusion, continuous schedule of reinforcement) in all heroin or saline SA rats (A, C) or each of the 3 groups (B, D). Three groups of animals: (1) H-RI, the heroin SA rats with “high” reinstatement induced by acute foot shock stress, n = 10; (2) L-RI, the heroin SA rats with “low” reinstatement induced by acute foot shock stress, n = 10; and (3) NR, the rats below the criterion for acquisition of heroin SA (20 infusions on days 5–7 of SA testing, 0.05 mg/kg/infusion), n = 6. * p<0.001 vs. Session 1 within the group; # p<0.05 vs. NR group.
Comparison of extinction and reinstatement behavioral responses. The same 3 groups of animals: (1) H-RI, the heroin SA rats with “high” reinstatement induced by acute foot shock stress, n = 10; (2) L-RI, the heroin SA rats with “low” reinstatement induced by acute foot shock stress, n = 10; and (3) NR, the rats below the criterion for acquisition of heroin SA, n = 6. The upper panels show the mean (sem) responses on the active lever (A) and inactive lever (B) during the four 3-h extinction sessions. * p<0.001 vs. Session 4 within the group; + p<0.05 vs. L-RI group; # p<0.05 vs. NR group. The middle panels (C, D) show individual responses and the lower panels (E, F) show the mean (sem) responses on both the active and inactive levers following exposure to 15-min intermittent foot shock stress (C, E) and to heroin (0.25 mg/kg, s.c.) (D, F) during the 3-h session of two reinstatement tests. * p<0.05 vs. inactive lever within the group; ++ p<0.001 vs. L-RI group; # p<0.05, ## p<0.01 vs. NR group.
(A) Comparison of arginine vasopressin (AVP) mRNA levels in the medial/basolateral amygdala (Me/BLA) and medial hypothalamus (MH). The same 3 groups of animals: (1) H-RI, the heroin SA rats with “high” reinstatement induced by acute foot shock stress; (2) L-RI, the heroin SA rats with “low” reinstatement induced by acute foot shock stress; and (3) NR, the rats below the criterion for acquisition of heroin SA (n=6–10). The dotted line represents basal mean mRNA level in each brain region of rats with saline SA without acute foot shock stress (heroin/stress control, n = 8). The panels show the mean (sem) mRNA levels (attomole/µg total RNA) measured 45 min after 15-min intermittent foot shock stress on day 16 (9 days after the last heroin SA). + p<0.05 vs. H-RI group; ## p<0.01 vs. NR group. (B) Regression of AVP mRNA levels in the Me/BLA and the foot shock stress-induced lever responding during 3-hour reinstatement session in the H-RI and L-RI rats. There was a significant correlation between the AVP mRNA level in the Me/BLA and the stress induced responding in all heroin SA rats, both the H-RI (•) (n = 10) and L-RI (○) animals (n = 10).
Comparison of pro-opiomelanocortin (POMC) mRNA levels in the medial hypothalamus (A) and orexin mRNA levels in the lateral hypothalamus (B). The same 3 groups of animals: (1) H-RI, the heroin SA rats with “high” reinstatement induced by acute foot shock stress; (2) L-RI, the heroin SA rats with “low” reinstatement induced by acute foot shock stress; and (3) NR, the rats below the criterion for acquisition of heroin SA (n = 6–9). The dotted line represents basal mean mRNA level for each gene in each brain region of the rats with saline SA without acute foot shock stress (heroin/stress control, n = 8). The panels show the mean (sem) mRNA levels (attomole/ug total RNA) measured 45 min after 15-min intermittent foot shock stress on day 16 (9 days after the last heroin SA). # p<0.05 vs. NR group.
Regression of dopamine D2 receptor mRNA levels in the caudate putamen (CPu) and foot shock stress-induced lever responding during 3-hour reinstatement session in the H-RI rats (heroin SA rats with “high” reinstatement induced by acute foot shock stress) and the L-RI rats (heroin SA rats with “low” reinstatement induced by acute foot shock stress). There was a significant correlation between the D2 mRNA level in the CPu and the stress induced responding in all heroin SA rats, both the H-RI (•) (n = 9) and L-RI (○) animals (n = 9).
No entities extracted from this document yet.
No uploaded files.
In this knowledge base
| Title | Year | PMID |
|---|---|---|
| The genetic epidemiology of substance use disorder: A review. | 2017 | 28938182 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Associations of the AVPR1A RS1 Microsatellite Locus with the Level of Hormones of the Anterior Pituitary Gland and Personality Traits. | Nakhodkin SS et al. | — | 2025 | → |
| Daily treatment with the dual orexin receptor antagonist DORA-12 during oxycodone abstinence decreases oxycodone conditioned reinstatement. | Illenberger JM et al. | — | 2023 | → |
| Effects of fentanyl self-administration on risk-taking behavior in male rats. | Wheeler AR et al. | — | 2023 | → |
| The effects of sleep restriction during abstinence on oxycodone seeking: Sex-dependent moderating effects of behavioral and hypothalamic-pituitary-adrenal axis-related phenotypes. | Olsen CM et al. | — | 2023 | → |
| Consideration of sex as a biological variable in the translation of pharmacotherapy for stress-associated drug seeking. | Martin EL et al. | — | 2021 | → |
| Evaluation of the relationship between the gene expression level of orexin-1 receptor in the rat blood and prefrontal cortex, novelty-seeking, and proneness to methamphetamine dependence: A candidate biomarker. | Tavakkolifard M et al. | — | 2020 | → |
| Targeting the Orexin System for Prescription Opioid Use Disorder. | Matzeu A et al. | — | 2020 | → |
| Brain and Cognition for Addiction Medicine: From Prevention to Recovery Neural Substrates for Treatment of Psychostimulant-Induced Cognitive Deficits. | D'Souza MS | — | 2019 | → |
| DRD2 and ANKK1 genes associate with late-onset heroin dependence in men. | Tsou CC et al. | — | 2019 | → |
| Anti-stress neuropharmacological mechanisms and targets for addiction treatment: A translational framework. | Greenwald MK | — | 2018 | → |
| Cocaine Self-administration Alters Transcriptome-wide Responses in the Brain's Reward Circuitry. | Walker DM et al. | — | 2018 | → |
| Modular organization of a hypocretin gene minimal promoter. | Sánchez-García A et al. | — | 2018 | → |
| Orexin A in men with heroin use disorder undergoing methadone maintenance treatment. | Tsai MC et al. | — | 2018 | → |
| The role of the vasopressin system and dopamine D1 receptors in the effects of social housing condition on morphine reward. | Bates MLS et al. | — | 2018 | → |
| Pharmacoepigenomics of opiates and methadone maintenance treatment: current data and perspectives. | Marie-Claire C et al. | — | 2017 | → |
| The amphetamine-associated context exerts a stronger motivational effect in low-anxiety rats than in high-anxiety rats. | Lehner M et al. | — | 2017 | → |
| The behavioral and molecular evaluation of effects of social instability stress as a model of stress-related disorders in adult female rats. | Nowacka-Chmielewska MM et al. | — | 2017 | → |
| The genetic epidemiology of substance use disorder: A review. | Prom-Wormley EC et al. | — | 2017 | → |
| Assessment of individual differences in the rat nucleus accumbens transcriptome following taste-heroin extended access. | Imperio CG et al. | — | 2016 | → |
| Combination of Levo-Tetrahydropalmatine and Low Dose Naltrexone: A Promising Treatment for Prevention of Cocaine Relapse. | Sushchyk S et al. | — | 2016 | → |
| Neuroscience of opiates for addiction medicine: From stress-responsive systems to behavior. | Zhou Y et al. | — | 2016 | → |
| Reward devaluation and heroin escalation is associated with differential expression of CRF signaling genes. | McFalls AJ et al. | — | 2016 | → |
| A Shared Molecular and Genetic Basis for Food and Drug Addiction: Overcoming Hypodopaminergic Trait/State by Incorporating Dopamine Agonistic Therapy in Psychiatry. | Gold MS et al. | — | 2015 | → |
| Low expression of D2R and Wntless correlates with high motivation for heroin. | Tacelosky DM et al. | — | 2015 | → |
| Predictors of heroin relapse: Personality traits, impulsivity, COMT gene Val158met polymorphism in a 5-year prospective study in Shanghai, China. | Su H et al. | — | 2015 | → |