Single housing during early adolescence causes time‐, area‐ and peptide‐specific alterations in endogenous opioids of rat brain

Granholm, Linnea; Roman, Erika; Nylander, Ingrid

doi:10.1111/bph.12753

Cited by 17 publications

(13 citation statements)

References 51 publications

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“…Short-term single housing, that is, 24 hours, mainly affected regions involved in the stress response, that is, pitui-tary, hypothalamus, amygdala, hippocampus, and cortex regions (Watts, 2000), which suggests that this is an acute stressor in both ages. A large impact of single housing on MEAP levels is in agreement with recent findings (Granholm et al, 2014). An increase in MEAP levels as seen here in the early stages of single housing could be an indicator of an activated stress-adapting system.…”

Section: Short-term Single Housing Alcohol Intake and Age-specific supporting

confidence: 93%

“…A large impact of single housing on MEAP levels is in agreement with recent findings (Granholm et al., 2014). An increase in MEAP levels as seen here in the early stages of single housing could be an indicator of an activated stress-adapting system.…”

Section: Discussionmentioning

confidence: 99%

“…Animal models of alcohol intake often involve single housing of the animals and this is of great concern for adolescent alcohol intake models because social isolation during this period have been shown to alter behavior and neurochemistry (Fone and Porkess, 2008) and increase alcohol intake in adulthood (Becker et al., 2011; Chappell et al., 2013). Social isolation in adolescent rats has also been shown to affect opioid peptide levels, particularly Met-enkephalin-Arg 6 Phe 7 (MEAP), in several brain areas (Granholm et al., 2014). Alcohol intake models based on social isolation during adolescence may therefore produce alcohol-induced effects confounded by the lack of social environment.…”

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confidence: 99%

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Alcohol‐Induced Changes in Opioid Peptide Levels in Adolescent Rats Are Dependent on Housing Conditions

Palm

Nylander

2014

Alcoholism Clin & Exp Res

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BackgroundEndogenous opioids are implicated in the mechanism of action of alcohol and alcohol affects opioids in a number of brain areas, although little is known about alcohol's effects on opioids in the adolescent brain. One concern, in particular when studying young animals, is that alcohol intake models often are based on single housing that may result in alcohol effects confounded by the lack of social interactions. The aim of this study was to investigate short- and long-term alcohol effects on opioids and the influence of housing conditions on these effects.MethodsIn the first part, opioid peptide levels were measured after one 24-hour session of single housing and 2-hour voluntary alcohol intake in adolescent and adult rats. In the second part, a model with a cage divider inserted during 2-hour drinking sessions was tested and the effects on opioids were examined after 6 weeks of adolescent voluntary intake in single-and pair-housed rats, respectively.ResultsThe effects of single housing were age specific and affected Met-enkephalin-Arg6Phe7 (MEAP) in particular. In adolescent rats, it was difficult to distinguish between effects induced by alcohol and single housing, whereas alcohol-specific effects were seen in dynorphin B (DYNB), beta-endorphin (BEND), and MEAP levels in adults. Voluntary drinking affected several brain areas and the majority of alcohol-induced effects were not dependent on housing. However, alcohol effects on DYNB and BEND in the amygdala were dependent on housing. Housing alone affected MEAP in the cingulate cortex.ConclusionsAge-specific housing- and alcohol-induced effects on opioids were found. In addition, prolonged voluntary alcohol intake under different housing conditions produced several alcohol-induced effects independent of housing. However, housing-dependent effects were found in areas implicated in stress, emotionality, and alcohol use disorder. Housing condition and age may therefore affect the reasons and underlying mechanisms for drinking and could potentially affect the outcome of a number of end points in research on alcohol intake.

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Section: Short-term Single Housing Alcohol Intake and Age-specific supporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Alcohol‐Induced Changes in Opioid Peptide Levels in Adolescent Rats Are Dependent on Housing Conditions

Palm

Nylander

2014

Alcoholism Clin & Exp Res

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“…The differences for adult vs. adolescent rats must be compared carefully as they could be due to age, ethanol administration model, or both. In both adult and adolescent rats, the central levels of endogenous opioids interact with housing conditions (i.e., single or group housed) and ethanol intake ( 19 , 20 ). These aforementioned studies show the profound importance of the experimental settings when working with ethanol models in rats.…”

Section: Discussionmentioning

confidence: 99%

“…To avoid biological littermates, the litters were cross-fostered and mixed on the day of birth (postnatal day, PND, 0) so each litter contained four females and six males. Previous studies have shown that single housing affects brain levels of endogenous opioid peptides in adolescent rats ( 19 , 20 ), so on PND 21 the pups were weaned and group housed (2–3 rats per cage) to avoid confounding factors.…”

Section: Methodsmentioning

confidence: 99%

Episodic Ethanol Exposure in Adolescent Rats Causes Residual Alterations in Endogenous Opioid Peptides

2018

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Adolescent binge drinking is associated with an increased risk of substance use disorder, but how ethanol affects the central levels of endogenous opioid peptides is still not thoroughly investigated. The aim of this study was to examine the effect of repeated episodic ethanol exposure during adolescence on the tissue levels of three different endogenous opioid peptides in rats. Outbred Wistar rats received orogastric (i.e., gavage) ethanol for three consecutive days per week between 4 and 9 weeks of age. At 2 h and 3 weeks, respectively, after the last exposure, beta-endorphin, dynorphin B and Met-enkephalin-Arg6Phe7 (MEAP) were analyzed with radioimmunoassay. Beta-endorphin levels were low in the nucleus accumbens during ethanol intoxication. Remaining effects of adolescent ethanol exposure were found especially for MEAP, with low levels in the amygdala, and high in the substantia nigra and ventral tegmental area three weeks after the last exposure. In the hypothalamus and pituitary, the effects of ethanol on beta-endorphin were dependent on time from the last exposure. An interaction effect was also found in the accumbal levels of MEAP and nigral dynorphin B. These results demonstrate that repeated episodic exposure to ethanol during adolescence affected opioid peptide levels in regions involved in reward and reinforcement as well as stress response. These alterations in opioid networks after adolescent ethanol exposure could explain, in part, the increased risk for high ethanol consumption later in life.

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Adolescent morphine exposure changes the endogenous vlPAG opioid response to inflammatory pain in rats

Alami,

Ghasemi,

Semnanian

et al. 2023

Developmental Psychobiology

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Adolescence is one of the most critical periods for brain development, and exposure to morphine during this period can have long‐life effects on pain‐related behaviors. The opioid system in the periaqueductal gray (PAG) is highly vulnerable to drug exposure. However, the impact of adolescent morphine exposure (AME) on the endogenous opioid system in the PAG is currently unknown. This study aims to investigate the long‐lasting effects of AME on the endogenous opioid system and its involvement in altering nociceptive behaviors. Adolescent rats were given escalating doses of morphine (2.5–25 mg/kg, subcutaneous) or an equal volume of saline twice daily for 10 consecutive days (PND 31–40). After a 30‐day washout period, adult rats underwent formalin tests following microinjection of morphine, naloxone, or saline into the ventrolateral PAG (vlPAG) region. The results indicated that morphine microinjection into the vlPAG of the adolescent morphine‐treated group significantly reduced the nociceptive score. However, the analgesic response to morphine in this group was significantly lower compared to the saline‐treated group during adolescence. Additionally, the nociceptive score significantly increased following naloxone but not saline microinjection into the vlPAG of the saline‐treated group during adolescence, rather than the morphine‐treated one. These findings indicate that AME has long‐lasting effects on the endogenous opioid system in the vlPAG, which can consequently alter behaviors related to inflammatory pain in adulthood.

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Single housing during early adolescence causes time‐, area‐ and peptide‐specific alterations in endogenous opioids of rat brain

Cited by 17 publications

References 51 publications

Alcohol‐Induced Changes in Opioid Peptide Levels in Adolescent Rats Are Dependent on Housing Conditions

Alcohol‐Induced Changes in Opioid Peptide Levels in Adolescent Rats Are Dependent on Housing Conditions

Episodic Ethanol Exposure in Adolescent Rats Causes Residual Alterations in Endogenous Opioid Peptides

Adolescent morphine exposure changes the endogenous vlPAG opioid response to inflammatory pain in rats

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