1.
Roman, Erika, et al.
(författare)
Short and prolonged periods of maternal separation and voluntary ethanol intake in male and female ethanol-preferring AA and ethanol-avoiding ANA rats
2005
Ingår i: Alcoholism. - 0145-6008 .- 1530-0277. ; 29:4, s. 591-601
Tidskriftsartikel (refereegranskat) abstract
BACKGROUND: Genetic as well as environmental factors can affect the propensity for psychopathology and/or drug dependence. Maternal separation represents an animal experimental model that is useful in studies of effects of early life experiences. The authors have established a protocol for short and prolonged periods of maternal separation to study adult neurochemistry, behavior, and ethanol intake and have previously reported alterations in ethanol intake in Wistar rats and ethanol-preferring rats. The aim of the current study was to more thoroughly study how early life experiences affect an inherited propensity for high and low ethanol intake, respectively, in male and female ethanol-preferring AA (Alko alcohol) and ethanol-avoiding ANA (Alko, Non-Alcohol) rats. METHODS: AA and ANA pups were assigned to one of three different rearing conditions: 15 min (MS15) or 360 min (MS360) of daily maternal separation in litters or normal animal facility rearing (AFR) during postnatal days 1 to 21. In adulthood, voluntary ethanol intake was investigated using the two-bottle free choice paradigm. RESULTS: In male ethanol-preferring AA rats, MS15 resulted in a lower intake and fewer high-preferring animals at 8% and 10% ethanol compared with MS360 rats. The male MS360 rats had a higher ethanol intake at 8% and 10% ethanol in comparison with AFR rats. In contrast, the female AA MS15 and MS360 rats had a lower ethanol intake and a lower preference for the 10% ethanol solution compared with the female AA AFR rats. In male and female ANA rats, no major separation-induced effects were found. CONCLUSIONS: The current results show that genetic inheritance can be affected by environmental manipulations in AA rats with an inherent high ethanol intake. The findings in female ethanol-preferring AA rats give further evidence of a differential outcome of maternal separation in male and female rats, as previously shown.
2.
Gustafsson, Lisa, et al.
(författare)
Ethanol-induced effects on opioid peptides in adult male Wistar rats are dependent on early environmental factors
2007
Ingår i: Neuroscience. - : Elsevier BV. - 0306-4522 .- 1873-7544. ; 146:3, s. 1137-1149
Tidskriftsartikel (refereegranskat) abstract
The vulnerability to develop alcoholism is dependent on both genetic and environmental factors. The neurobiological mechanisms underlying these factors are not fully understood but individual divergence in the endogenous opioid peptide system may contribute. We have previously reported that early-life experiences can affect endogenous opioids and also adult voluntary ethanol intake. In the present study, this line of research was continued and the effects of long-term voluntary ethanol drinking on the opioid system are described in animals reared in different environmental settings. Rat pups were subjected to 15 min (MS15) or 360 min (MS360) of daily maternal separation during postnatal days 1–21. At 10 weeks of age, male rats were exposed to voluntary ethanol drinking in a four-bottle paradigm with 5%, 10% and 20% ethanol solution in addition to water for 2 months. Age-matched controls received water during the same period. Immunoreactive (ir) Met-enkephalin-Arg6Phe7 (MEAP) and dynorphin B (DYNB) peptide levels were thereafter measured in the pituitary gland and several brain areas. In water-drinking animals, lower ir MEAP levels were observed in the MS360 rats in the hypothalamus, medial prefrontal cortex, striatum and the periaqueductal gray, whereas no differences were seen in ir DYNB levels. Long-term ethanol drinking induced lower ir MEAP levels in MS15 rats in the medial prefrontal cortex and the periaqueductal gray, whereas higher levels were detected in MS360 rats in the hypothalamus, striatum and the substantia nigra. Chronic voluntary drinking affected ir DYNB levels in the pituitary gland, hypothalamus and the substantia nigra, with minor differences between MS15 and MS360. In conclusion, manipulation of the early environment caused changes in the opioid system and a subsequent altered response to ethanol. The altered sensitivity of the opioid peptides to ethanol may contribute to the previously reported differences in ethanol intake between MS15 and MS360 rats.
3.
Gustafsson, Lisa, et al.
(författare)
The impact of postnatal environment on opioid peptides in young and adult male Wistar rats
2008
Ingår i: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 42:2, s. 177-191
Tidskriftsartikel (refereegranskat) abstract
Early environmental influences can change the neuronal development and thereby affect behavior in adult life. The aim in the present study was to thoroughly examine the impact of early environmental factors on endogenous opioids by using a rodent maternal separation (MS) model. The endogenous opioid peptide system is not fully developed at birth, and short- and/or long-term alterations may occur in these neural networks in animals exposed to manipulation of the postnatal environment. Rat pups were subjected to one of five rearing conditions; 15 min (MS15) litter (l) or individual (i), 360 min (MS360) l or i daily MS, or housed under normal animal facility rearing (AFR) conditions during postnatal days 1-21. Measurements of immunoreactive (ir) Met-enkephalin-Arg(6)Phe(7) (MEAP) and dynorphin B (DYNB) peptide levels in the pituitary gland and in a number of brain areas, were performed at three and 10 weeks of age, respectively. MS-induced changes were more pronounced in ir MEAP levels, especially in individually separated rats at three weeks of age and in litter-separated rats at 10 weeks of age. The enkephalin and dynorphin systems have different developmental patterns, dynorphin appearing earlier, which may point at a more sensitive enkephalin system during the early postnatal weeks. The results provide evidence that opioid peptides are sensitive for early environmental factors and show that the separation conditions are critical and also result in changes manifesting at different time points. MS-induced effects were observed in areas related to stress, drug reward and dependence mechanisms. By describing effects on opioid peptides, the study addresses the possible role of a deranged endogenous opioid system in the previously described behavioral consequences of MS.
4.
Ploj, Karolina, et al.
(författare)
Basal levels and alcohol-induced changes in nociceptin/orphanin FQ, dynorphin, and enkephalin levels in C57BL/6J mice
2000
Ingår i: Brain Research Bulletin. - 0361-9230 .- 1873-2747. ; 53:2, s. 219-226
Tidskriftsartikel (refereegranskat) abstract
In order to investigate the involvement of the opioid and nociceptin/orphanin FQ (N/OFQ) system in alcohol drinking behaviour, N/OFQ and the opioid peptides dynorphin B (DYNB) and Met-enkephalin-Arg(6) Phe(7) (MEAP) were examined in the alcohol-preferring C57BL/6J mice. Basal peptide levels were compared in the brain and the pituitary gland with basal levels in the alcohol-avoiding DBA/2J mice. Furthermore, the effects of chronic alcohol self-administration on peptides were studied in the C57BL/6J mice. Compared to the DBA/2J mice, C57BL/6J mice had low immunoreactive (ir) levels of DYNB and MEAP in the nucleus accumbens, the hippocampus, and the substantia nigra, low ir-DYNB levels in the striatum and low ir-MEAP levels in the frontal cortex. Higher ir-DYNB levels in the pituitary gland and in the periaqueductal gray (PAG) and higher ir-N/OFQ levels in the frontal cortex and in the hippocampus were detected in C57BL/6J mice compared to the DBA/2J mice. After 4 weeks of voluntary alcohol consumption, only minor changes in steady-state peptide levels were identified. However, 5 days after the alcohol-drinking period, lower levels of all peptides were detected in the ventral tegmental area and ir-DYNB levels were also lower in the amygdala and in the substantia nigra. Twenty-one days after cessation of alcohol self-administration, the opioid peptides in alcohol-consuming C57BL/6J mice were lower in the PAG, the N/OFQ was lower in the frontal cortex and DYNB was higher in the amygdala and substantia nigra as compared to control C57BL/6J mice. This study demonstrates strain differences between C57BL/6J mice and DBA/2J mice that could contribute to divergent drug-taking behaviour, and it also demonstrates time- and structure-specific changes in neuropeptide levels after alcohol self-administration in the C57BL/6J mice.
5.
Roman, Erika, et al.
(författare)
Behavioral profiles and stress-induced corticosteroid secretion in male Wistar rats subjected to short and prolonged periods of maternal separation
2006
Ingår i: Hormones and Behavior. - : Elsevier BV. - 0018-506X .- 1095-6867. ; 50:5, s. 736-747
Tidskriftsartikel (refereegranskat) abstract
Early life experiences are important for the development of neurobiobehavioral mechanisms and subsequent establishment of mental functions. In experimental animals, early life experiences can be studied using the maternal separation model. Maternal separation has been described to induce neurobiological changes and thus affect brain function, mental state and behavior. We have established a protocol in order to study the effects of repeated short and prolonged periods of maternal separation during the postnatal period on adult neurochemistry, voluntary ethanol intake and behavior. In the present experiment, we focus on the long-term effects of maternal separation on exploration and risk assessment behavior as well corticosteroid secretion. Rat pups were assigned to 15 min (MS15) or 360 min (MS360) of daily maternal separation and normal animal facility rearing (AFR) during postnatal days 1-21. To establish the adult behavioral profile in male rats, three tests were used: the Concentric Square Field (CSF), the Open Field (OF) and the Elevated Plus-maze (EPM). No differences between the three experimental groups were found in the traditional OF and EPM tests. The CSF test indicated that the MS360 rats were more explorative and expressed an altered risk assessment and risk-taking profile. In response to a restraint stress, MS360 rats had a blunted corticosterone release in contrast to MS15 and AFR rats. In contrast to previous results, the outcome of the present investigation does not support the notion that a prolonged period of maternal separation results in an adult phenotype characterized by an increased emotional reactivity.
6.
Roman, Erika, et al.
(författare)
Variations in opioid peptide levels during the estrous cycle in Sprague-Dawley rats
2006
Ingår i: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 40:3, s. 195-206
Tidskriftsartikel (refereegranskat) abstract
The estrous cycle, with its various hormonal conditions, may provide us with the means of understanding how endocrine states relate to opioid mechanisms. There has been increasing experimental support for interaction between sex steroids and opioid peptides in the central nervous system. Here, we describe fluctuations in endogenous brain immunoreactive (ir) peptide levels during various phases of the estrous cycle in the female Sprague-Dawley rat. Ir levels of dynorphin A, dynorphin B, Leu-enkephalin-Arg(6), Met-enkephalin-Arg(6)Phe(7) and nociceptin/orphanin FQ were measured in the pituitary gland and in 10 areas of the brain during the diestrus, proestrus and estrus phase. In several areas of the brain, basal levels of endogenous opioid peptides showed variation during the course of the estrous cycle. Significant differences were found between the diestrus state and the proestrus and/or estrus conditions, particularly in the nucleus accumbens, caudate putamen and the substantia nigra. The ir levels of the endogenous peptide nociceptin/orphanin FQ became altered in only one of the areas measured, indicating less variance during the estrous cycle. Correlation analyses revealed that significant associations between dynorphin A or dynorphin B and Leu-enkephalin-Arg(6) were found more often during estrus than during the diestrus and proestrus conditions. The ratio between the ir levels of Leu-enkephalin-Arg(6), a cleavage product of the enzymatic conversion of dynorphin peptides into shorter peptides in vivo, and dynorphin peptides was calculated. The significantly lower ratio between Leu-enkephalin-Arg(6) and dynorphin B in diestrus than in proestrus and estrus also indicates cyclic fluctuations in the enzymatic cleavage of dynorphin. These findings are discussed in relation to the possible role of interactions between sex steroids and opioid peptide mechanisms during the normal estrous cycle.
7.
Engel, Jörgen, 1942, et al.
(författare)
A ghrelin receptor (GHS-R1A) antagonist attenuates the rewarding properties of morphine and increases opioid peptide levels in reward areas in mice
2015
Ingår i: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X .- 1873-7862. ; 25:12, s. 2364-2371
Tidskriftsartikel (refereegranskat) abstract
Gut-brain hormones such as ghrelin have recently been suggested to have a role in reward regulation. Ghrelin was traditionally known to regulate food intake and body weight homoeostasis. In addition, recent work has pin-pointed that this peptide has a novel role in drug-induced reward, including morphine-induced increase in the extracellular levels of accumbal dopamine in rats. Herein the effect of the ghrelin receptor (GHS-R1A) antagonist, JMV2959, on morphine-induced activation of the mesolimbic dopamine system was investigated in mice. In addition, the effects of JMV2959 administration on opioid peptide levels in reward related areas were investigated. In the present series of experiment we showed that peripheral JMV2959 administration, at a dose with no effect per se, attenuates the ability of morphine to cause locomotor stimulation, increase the extracellular levels of accumbal dopamine and to condition a place preference in mice. JMV2959 administration significantly increased tissue levels of Metenkephalin-Arg(6)Phe(7) in the ventral tegmental area, dynorphin B in hippocampus and Leuenkephalin-Arg(6) in striatum. We therefore hypothesise that JMV2959 prevents morphine-induced reward via stimulation of delta receptor active peptides in striatum and ventral tegmental areas. In addition, hippocampal peptides that activate kappa receptor may be involved in JMV2959's ability to regulate memory formation of reward. Given that development of drug addiction depends, at least in part, of the effects of addictive drugs on the mesolimbic dopamine system the present data suggest that GIS-R1A antagonists deserve to be elucidated as novel treatment strategies of opioid addiction.
8.
Granholm, Linnea, et al.
(författare)
Single housing during early adolescence causes time-, area- and peptide-specific alterations in endogenous opioids of rat brain
2015
Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 172:2, s. 606-614
Tidskriftsartikel (refereegranskat) abstract
BACKGROUND AND PURPOSE: A number of experimental procedures require single housing to assess individual behaviour and physiological responses to pharmacological treatments. The endogenous opioids are closely linked to social interaction, especially early in life, and disturbance in the social environment may affect opioid peptides and thereby confound experimental outcome. The aim of the present study was to examine time-dependent effects of single housing on opioid peptides in rats.EXPERIMENTAL APPROACH: Early adolescent Sprague Dawley rats (post-natal day 22) were subjected to either prolonged (7 days) or short (30 min) single housing. Several brain regions were dissected and immunoreactive levels of Met-enkephalin-Arg(6) Phe(7) (MEAP), dynorphin B and nociception/orphanin FQ, as well as serum corticosterone were measured using RIA.KEY RESULTS: Prolonged single housing reduced immunoreactive MEAP in hypothalamus, cortical regions, amygdala, substantia nigra and periaqueductal grey. Short single housing resulted in an acute stress response as indicated by high levels of corticosterone, accompanied by elevated immunoreactive nociceptin/orphanin FQ in medial prefrontal cortex, nucleus accumbens and amygdala. Neither short nor prolonged single housing affected dynorphin B.CONCLUSIONS AND IMPLICATIONS: Disruption in social environmental conditions of rats, through single housing during early adolescence, resulted in time-, area- and peptide-specific alterations in endogenous opioids in the brain. These results provide further evidence for an association between early life social environment and opioids. Furthermore, the results have implications for experimental design; in any pharmacological study involving opioid peptides, it is important to distinguish between effects induced by housing and treatment.
9.
Lundberg, Stina, 1990-
(författare)
Adolescent behavior : Links to early-life stress and alcohol in male and female rats
2020
Doktorsavhandling (övrigt vetenskapligt/konstnärligt) abstract
Adolescence is an important developmental phase with large changes in behavior, physiology and neurobiology, which transform an individual from immature child to independent adult. Due to these changes, adolescence is a sensitive period for exposure to environmental factors such as stress and drug exposure; it is also a common age of onset for alcohol consumption as well as several psychiatric disorders. Despite these factors, less is known about this developmental period than regarding adult individuals. Behavior is regulated by the central nervous system and can be used as a lens to study these processes as well as for examination of associations between individual differences, early-life stress and alcohol. The aim of this thesis was to experimentally examine adolescent behavior and its links to early-life stress and alcohol in adolescent male and female rats. Different behavioral tests were used to profile adolescent animals together with animal models of early-life stress, voluntary alcohol consumption and alcohol exposure. In addition, stress responsiveness after early-life stress and the impact of alcohol exposure on endogenous opioid peptide levels as well as blood alcohol concentrations were examined. The adolescent behavioral profile in the multivariate concentric square field™ (MCSF) was characterized and validated against the elevated plus maze and open field tests. The main finding was subgroups based on individual variation that revealed three distinct behavioral types: Explorers, Shelter seekers and Main type animals. This pattern was replicated in an additional, independent cohort. Early-life stress, modelled by prolonged maternal separation, showed small effects on behavior in the MCSF and on social play behavior. However, an effect on stress responsiveness in males but not females subjected to prolonged maternal separation was discovered. Predisposition for high alcohol consumption did not have a shared behavioral profile among selectively bred rat lines. However, a subgroup of high drinking individuals in an outbred cohort showed behavioral similarities to one of the selectively bred lines. Alcohol exposure showed small, but sex-dependent, effects on behavior and endogenous opioid peptide levels. Together, these studies provide new information about adolescent behavior and associations to early-life stress and alcohol in males and females, relationships not extensively studied in adolescence.
10.
