scholarly journals Chronic Fentanyl Self-Administration Generates a Shift toward Negative Affect in Rats during Drug Use

2021 ◽  
Vol 11 (8) ◽  
pp. 1064
Author(s):  
Angela N. Dao ◽  
Nicholas J. Beacher ◽  
Vivian Mayr ◽  
Annalisa Montemarano ◽  
Sam Hammer ◽  
...  
Keyword(s):  
Drug Use ◽  
Negative Affect ◽  
Positive Affect ◽  
Chronic Exposure ◽  
Negative Reinforcement ◽  
Affective State ◽  
Sprague Dawley ◽  
Self Administration ◽  
Initial Exposure ◽  
Long Access

Drug addiction is thought to be driven by negative reinforcement, and it is thought that a shift from positive affect upon initial exposure to negative affect after chronic exposure to a drug is responsible for maintaining self-administration (SA) in addicted individuals. This can be modeled in rats by analyzing ultrasonic vocalizations (USVs), a type of intraspecies communication indicative of affective state based on the frequency of the emission: calls in the 22 kHz range indicate negative affect, whereas calls in the 50 kHz range indicate positive affect. We employed a voluntary chronic, long-access model of fentanyl SA to analyze affective changes in the response to chronic fentanyl exposure. Male Sprague-Dawley rats self-administered either fentanyl (N = 7) or saline (N = 6) for 30 consecutive days and USVs were recorded at four different time points: the day before first SA session (PRE), the first day of SA (T01), the last day of SA (T30), and the first day of abstinence (ABS). At T01, the ratio of 50 to 22 kHz calls was similar between the fentanyl and saline groups, but at T30, the ratio differed between groups, with the fentanyl group showing significantly fewer 50 kHz calls and more 22 kHz calls relative to saline animals. These results indicate a shift toward a negative affect during drug use after chronic exposure to fentanyl and support negative reinforcement as a main driving factor of opioid addiction.

scholarly journals Extended access self-administration of methamphetamine is associated with age- and sex-dependent differences in drug taking behavior and recognition memory deficits in rats

2019 ◽  
Author(s):  
Sara R. Westbrook ◽  
Megan R. Dwyer ◽  
Laura R. Cortes ◽  
Joshua M. Gulley
Keyword(s):  
Nmda Receptor ◽  
Drug Use ◽  
Expression Profiles ◽  
D1 Receptor ◽  
Receptor Expression ◽  
Cognitive Test ◽  
Adult Onset ◽  
Sprague Dawley ◽  
Self Administration ◽  
Long Access

AbstractIndividuals who begin drug use during early adolescence experience more adverse consequences compared to those initiating later, especially if they are female. The mechanisms for these age and gender differences remain obscure, but studies in rodents suggest that psychostimulants may disrupt the normal ontogeny of dopamine and glutamate systems in the prefrontal cortex (PFC). Here, we studied Sprague-Dawley rats of both sexes who began methamphetamine (METH, i.v.) self-administration (SA) in adolescence (postnatal [P] day 41) or adulthood (P91). Rats received seven daily 2-h SA sessions with METH or saccharin as the reinforcer, followed by 14 daily long access (LgA; 6 h) sessions. After 7 and 14 days of abstinence, novel object (OR) or object-in-place (OiP) recognition was assessed. PFC and nucleus accumbens were collected 7 days after the final cognitive test and NMDA receptor subunits and dopamine D1 receptor expression was measured. We found that during LgA sessions, adolescent-onset rats escalated METH intake more rapidly than adult-onset rats, with adolescent-onset females earning the most infusions. Adolescent-onset rats exhibited modest deficits in OiP compared to adult-onset rats, but there was no sex difference in this effect and no groups differed in OR. We found no group differences in D1 and NMDA receptor expression, suggesting no long-lasting alteration of ontogenetic expression profiles. Our findings suggest that adolescent-onset drug use is more likely to lead to compulsive-like patterns of drug-taking and subsequent dysfunction of PFC-dependent cognition.

scholarly journals Spontaneous and Naloxone-Precipitated Withdrawal Behaviors From Chronic Opiates are Accompanied by Changes in N-Oleoylglycine and N-Oleoylalanine Levels in the Brain and Ameliorated by Treatment With These Mediators

2021 ◽  
Vol 12 ◽  
Author(s):  
Samantha M. Ayoub ◽  
Fabiana Piscitelli ◽  
Cristoforo Silvestri ◽  
Cheryl L. Limebeer ◽  
Erin M. Rock ◽  
...  
Keyword(s):  
Steady State ◽  
Nucleus Accumbens ◽  
Chronic Exposure ◽  
Insular Cortex ◽  
Morphine Withdrawal ◽  
Opiate Withdrawal ◽  
Microbiota Composition ◽  
Sprague Dawley ◽  
Self Administration ◽  
Colonic Microbiota

Rationale: The endocannabinoidome mediators, N-Oleoylglycine (OlGly) and N-Oleoylalanine (OlAla), have been shown to reduce acute naloxone-precipitated morphine withdrawal affective and somatic responses.Objectives: To determine the role and mechanism of action of OlGly and OlAla in withdrawal responses from chronic exposure to opiates in male Sprague-Dawley rats.Methods: Opiate withdrawal was produced: 1) spontaneously 24 h following chronic exposure to escalating doses of morphine over 14 days (Experiments 1 and 2) and steady-state exposure to heroin by minipumps for 12 days (Experiment 3), 2) by naloxone injection during steady-state heroin exposure (Experiment 4), 3) by naloxone injection during operant heroin self-administration (Experiment 5).Results: In Experiment 1, spontaneous morphine withdrawal produced somatic withdrawal reactions. The behavioral withdrawal reactions were accompanied by suppressed endogenous levels of OlGly in the nucleus accumbens, amygdala, and prefrontal cortex, N-Arachidonylglycerol and OlAla in the amygdala, 2-arachidonoylglycerol in the nucleus accumbens, amygdala and interoceptive insular cortex, and by changes in colonic microbiota composition. In Experiment 2, treatment with OlAla, but not OlGly, reduced spontaneous morphine withdrawal responses. In Experiment 3, OlAla attenuated spontaneous steady-state heroin withdrawal responses at both 5 and 20 mg/kg; OlGly only reduced withdrawal responses at the higher dose of 20 mg/kg. Experiment 4 demonstrated that naloxone-precipitated heroin withdrawal from steady-state exposure to heroin (7 mg/kg/day for 12 days) is accompanied by tissue-specific changes in brain or gut endocannabinoidome mediator, including OlGly and OlAla, levels and colonic microbiota composition, and that OlAla (5 mg/kg) attenuated behavioural withdrawal reactions, while also reversing some of the changes in brain and gut endocannabinoidome and gut microbiota induced by naloxone. Experiment 5 demonstrated that although OlAla (5 mg/kg) did not interfere with operant heroin self-administration on its own, it blocked naloxone-precipitated elevation of heroin self-administration behavior.Conclusion: These results suggest that OlAla and OlGly are two endogenous mediators whose brain concentrations respond to chronic opiate treatment and withdrawal concomitantly with changes in colon microbiota composition, and that OlAla may be more effective than OlGly in suppressing chronic opiate withdrawal responses.

Neuroticism, alexithymia, negative affect and positive affect as predictors of medically unexplained symptoms in primary care

2002 ◽  
Vol 14 (4) ◽  
pp. 181-185 ◽  
Author(s):  
V. De Gucht
Keyword(s):  
Primary Care ◽  
Negative Affect ◽  
Positive Affect ◽  
Personality Traits ◽  
Affective State ◽  
Medically Unexplained Symptoms ◽  
Positive And Negative Affect ◽  
Medically Unexplained ◽  
Unexplained Symptoms

Background:Somatization has been defined in a number of ways. Despite their differences, these definitions have one element in common, namely the presence of somatic symptoms that cannot be explained (adequately) by organic findings.Objective:The primary objectives of the dissertation were to gain a better insight into the concept of somatization, and to study (prospectively) the relationship between neuroticism and alexithymia, two personality traits that have been shown to be related to somatization, the affective state dimensions positive and negative affect (or psychological distress) and medically unexplained symptoms.Method:A selective review was conducted regarding conceptual and methodological issues related to somatization. A total number of 318 patients, presenting to their primary care physician with medically unexplained symptoms, participated in the prospective study. Both at baseline and at 6-month follow-up a number of measures were filled out with respect to somatization, neuroticism, alexithymia, negative and positive affect, anxiety and depression.Results:The concept of somatization was clarified, thereby making use of the distinction between presenting and functional somatization. The personality traits neuroticism and alexithymia were found to have an indirect influence on symptom reports. Both the cross-sectional and follow-up data pointed to the importance of positive and negative affect as determinants of (changes in) number of symptoms (over time). Negative affect, together with the alexithymia dimension measuring difficulty identifying feelings, predicted symptom persistence.Conclusions:The theoretical as well as therapeutic implications of the present paper may give an impetus to new research in the domain of somatization.

scholarly journals Incentive and dopamine sensitization produced by intermittent but not long access cocaine self-administration

2018 ◽  
Author(s):  
Alex B. Kawa ◽  
Alec C. Valenta ◽  
Robert T. Kennedy ◽  
Terry E. Robinson
Keyword(s):  
Nucleus Accumbens ◽  
Drug Use ◽  
In Vivo Microdialysis ◽  
Group Differences ◽  
Self Administration ◽  
The Core ◽  
Intermittent Access ◽  
High Motivation ◽  
Long Access

Recent studies suggest that the temporal pattern of drug use (pharmacokinetics) has a profound effect on the ability of self-administered cocaine to produce addiction-like behavior in rodents, and to change the brain. To further address this issue, we compared the effects of Long Access (LgA) cocaine self-administration, which is widely used to model the transition to addiction, with Intermittent Access (IntA), which is thought to better reflect the pattern of drug use in humans, on the ability of self-administered cocaine to increase dopamine (DA) overflow in the core of the nucleus accumbens (using in vivo microdialysis), and to produce addiction-like behavior. IntA experience was more effective than LgA in producing addiction-like behavior- a drug experience-dependent increase in motivation for cocaine assessed using behavioral economic procedures, and cue-induced reinstatement, despite much less total drug consumption. There were no group differences in basal levels of DA in dialysate, but a single self-administered IV injection of cocaine increased DA in the core of the nucleus accumbens to a greater extent in rats with prior IntA experience than those with LgA or Short Access (ShA) experience, and the latter two groups did not differ. Furthermore, high motivation for cocaine was associated with a high DA response. Thus, IntA, but not LgA, produced both incentive and DA sensitization. This is consistent with the notion that a hyper-responsive dopaminergic system may contribute to the transition from casual patterns of drug use to the problematic patterns that define addiction.

scholarly journals Does Affect Influence Coping Styles among People from North India During the Pandemic? Implications for Psychological Well-Being

2021 ◽  
Author(s):  
Shreya Verma ◽  
Meetu Khosla ◽  
Garima Goel
Keyword(s):  
Negative Affect ◽  
Positive Affect ◽  
Coping Styles ◽  
Affective State ◽  
Well Being ◽  
North India ◽  
Positive And Negative Affect ◽  
Psychological Well Being ◽  
Coping Scale ◽  
Males And Females

Does affect influence coping styles among people from North India during the COVID pandemic? This study investigates how affective state influences the coping styles of people from North India and to examine its impact on psychological well-being. Coping styles, PA, negative affect, and psychological well-being of the sample (n=220; 105 males (46%) and 115 females (53.5%)) (Mean Age= 30.75) (SD= 15.36 years) were analysed during the pandemic. Coping styles were assessed using the Coping Scale (Hamby, Grych, & Banyard, 2013), psychological well-being was assessed using the Ryff Scale of Psychological Well-Being (Ryff and Keyes, 1995) and affect was evaluated using The Positive and Negative Affect Schedule (PANAS) (Watson, Clark, & Tellengen, 1988). The findings revealed that coping was positively related to psychological well-being but negatively related to Negative Affect (NA). Positive Affect (PA) was positively related to psychological well-being but negatively related to coping. Additionally, significant differences were seen in the PA and negative affect of males and females. Implications of psychological well-being are further discussed.

scholarly journals Empirical validation of the integrative psychological group intervention for women with breast cancer - preliminary results

2019 ◽  
Vol 76 (10) ◽  
pp. 1022-1028 ◽  
Author(s):  
Ivana Novakov ◽  
Svetlana Popovic-Petrovic ◽  
Tihomir Dugandzija ◽  
Milanka Tatic
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Negative Affect ◽  
Positive Affect ◽  
Group Intervention ◽  
Affective State ◽  
Cancer Surgery ◽  
T Test ◽  
Breast Cancer Surgery ◽  
Symptoms Of Depression

Background/Aim. Breast cancer diagnosis is an extremely stressful life event that brings a number of physical and psychological challenges. However, supportive and psychoeducational group interventions can significantly decrease psychological distress in patients. The aim of this study was to empirically validate the effects of the integrative psychological group intervention, regarding the affective state of women who underwent breast cancer surgery at the Oncology Institute of Vojvodina. Methods. This study was conducted on a sample of 30 women, with the average age of 53.17 years (standard deviation ? SD = 10.09). Following the surgical intervention, the inpatients participated in an integrative group session consisting of the following parts: 1) supportive-expressive, 2) psycho-educational and 3) healtheducational. Before the session, participants filled in a demographic data questionnaire, measures of positive and negative affect (PANAS), optimism (LOT-R), hope (AHS), neuroticism (BFI) and symptoms of depression (DASS-21). At the end of the group sessions, the participants filled in the PANAS again. Results. A paired-samples t-test showed that following an intervention, a statistically significant increase in positive affect had occurred (t(29) = -4.44, p < 0.001). For negative affect, the t-test also yields the statistically significant results (t(29) = 5.60, p < 0.001), showing that intervention led to a significant decrease in negative affect. The nonparametric Wilcoxon Signed-Rank test also confirmed these results. The multiple regression analysis (F (4, 25) = 3.46, p = 0.02) showed that high neuroticism and low symptoms of depression significantly predicted a greater increase in positive affect following the session. Another regression analysis (F (4, 25) = 3.32, p = 0.03) showed that the higher symptoms of depression and, marginally, higher hope significantly predicted a greater decrease in negative affect. Conclusion. Our results showed that the integrative psychological group intervention had positive short-term effects regarding the affective state of women who underwent breast cancer surgery, and that different psychological variables can play a significant role in prediction of changes in patients? affect.

Affective Outcomes of Intramural Sport Participation

2015 ◽  
Vol 39 (1) ◽  
pp. 69-81 ◽  
Author(s):  
Evan Webb ◽  
Scott Forrester
Keyword(s):  
Negative Affect ◽  
Positive Affect ◽  
Sport Participation ◽  
Affective State ◽  
Well Being ◽  
Task Orientation ◽  
Subjective Well Being ◽  
Psychological Benefits ◽  
Affective Outcomes ◽  
Intramural Sport

Participation in collegiate intramural sports provides numerous, positive psychological benefits for its participants. Benefits of participation in intramural programs include improved happiness and subjective well-being which can be operationalized as one's positive affective state. The purpose of this study was to determine the affective outcomes (positive and negative affect) of intramural sport participation in a collegiate setting. Students at a Canadian university ( N = 315) completed a questionnaire immediately following their participation in an intramural sport. Overall, and across all demographic variables, participants reported significantly higher levels of positive affect than negative affect, even for all levels of task- or ego-orientation (low, medium, and high). A MANOVA revealed significant differences between the three levels of task-orientation on positive affect but not negative affect. These results are promising indicators of students' continued sport participation on campus and later in life as intramural sport participants report experiencing significantly more positive affect than negative affect.

scholarly journals Oxycodone self-administration activates the mitogen-activated protein kinase/ mitogen- and stress-activated protein kinase (MAPK-MSK) signaling pathway in the rat dorsal striatum

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christopher A. Blackwood ◽  
Michael T. McCoy ◽  
Bruce Ladenheim ◽  
Jean Lud Cadet
Keyword(s):  
Protein Kinase ◽  
Histone H3 ◽  
Dorsal Striatum ◽  
Mitogen Activated Protein Kinase ◽  
Sprague Dawley ◽  
Self Administration ◽  
Molecular Analyses ◽  
Sprague Dawley Rats ◽  
Mitogen Activated Protein ◽  
Long Access

AbstractTo identify signaling pathways activated by oxycodone self-administration (SA), Sprague–Dawley rats self-administered oxycodone for 20 days using short—(ShA, 3 h) and long-access (LgA, 9 h) paradigms. Animals were euthanized 2 h after SA cessation and dorsal striata were used in post-mortem molecular analyses. LgA rats escalated their oxycodone intake and separated into lower (LgA-L) or higher (LgA-H) oxycodone takers. LgA-H rats showed increased striatal protein phosphorylation of ERK1/2 and MSK1/2. Histone H3, phosphorylated at serine 10 and acetylated at lysine 14 (H3S10pK14Ac), a MSK1/2 target, showed increased abundance only in LgA-H rats. RT-qPCR analyses revealed increased AMPA receptor subunits, GluA2 and GluA3 mRNAs, in the LgA-H rats. GluA3, but not GluA2, mRNA expression correlated positively with changes in pMSK1/2 and H3S10pK14Ac. These findings suggest that escalated oxycodone SA results in MSK1/2-dependent histone phosphorylation and increases in striatal gene expression. These observations offer potential avenues for interventions against oxycodone addiction.

scholarly journals Oxycodone self-administration activates the mitogen-activated protein kinase/mitogen- and stress-activated protein kinase (MAPK-MSK) signaling pathway in the rat dorsal striatum

2020 ◽  
Author(s):  
Christopher A. Blackwood ◽  
Michael T. McCoy ◽  
Bruce Ladenheim ◽  
Jean Lud Cadet
Keyword(s):  
Protein Kinase ◽  
Histone H3 ◽  
Dorsal Striatum ◽  
Mitogen Activated Protein Kinase ◽  
Sprague Dawley ◽  
Self Administration ◽  
Pharmacological Interventions ◽  
Sprague Dawley Rats ◽  
Mitogen Activated Protein ◽  
Long Access

ABSTRACTTo identify signaling pathways activated by oxycodone self-administration (SA), Sprague-Dawley rats self-administered oxycodone for 20 days using short-access (ShA, 3 h) and long-access (LgA, 9 h) paradigms. Animals were euthanized two hours after SA cessation and dorsal striata were used in post-mortem molecular analyses. LgA rats escalated their oxycodone intake and separated into lower (LgA-L) or higher (LgA-H) oxycodone takers. LgA-H rats showed increased striatal protein phosphorylation of ERK1/2 and MSK1/2. Histone H3, phosphorylated at serine 10 and acetylated at lysine 14 (H3S10pK14Ac), a MSK1/2 target, showed increased abundance only in LgA-H rats. RT-qPCR analyses revealed increased AMPA receptor subunits, GluA2 and GluA3 mRNAs in the LgA-H rats. GluA3, but not GluA2, expression correlated positively with changes in pMSK1/2 and H3S10pK14Ac. Our findings indicate that escalated oxycodone SA results in MSK1/2-dependent histone phosphorylation, which promoted increases in striatal gene expression. Our observations offer novel avenues for pharmacological interventions against oxycodone addiction.

scholarly journals Paradoxical changes in brain reward status during opioid self-administration in a novel test of the negative reinforcement hypothesis

2018 ◽  
Author(s):  
Jacques D. Nguyen ◽  
Yanabel Grant ◽  
Michael A. Taffe
Keyword(s):  
Negative Reinforcement ◽  
Affective State ◽  
Kappa Opioid Receptor ◽  
Opioid Antagonist ◽  
Prescription Opioid ◽  
Opioid Use ◽  
Self Administration ◽  
Kappa Opioid ◽  
Brain Reward ◽  
Negative Affective State

ABSTRACTBackground and PurposeThe extra-medical use and addiction of prescription opioid analgesics is a growing health problem. To characterize how prescription opioid abuse develops, this study investigated the affective consequences of escalating prescription opioid use using intracranial self-stimulation (ICSS) reward and oxycodone intravenous self-administration (IVSA) models.Experimental ApproachMale Wistar rats were given access to oxycodone IVSA (0.15 mg/kg/infusion, i.v.) in Short Access (ShA; 1 h) or Long Access (LgA; 12 h) sessions for 5 sessions/week followed by intermittent 60 h discontinuations from drug access, a novel explicit test of the negative reinforcement hypothesis. A separate group was first trained in the ICSS procedure and then in oxycodone IVSA in 11 h LgA sessions.Key ResultsRats given LgA to oxycodone escalated their responding more than ShA rats, with significant increases following 60 h discontinuations. Pre-session brain reward thresholds increased with sequential daily LgA IVSA sessions, consistent with a growing negative affective state consequent to successive daily intoxication/abstinence cycles. A 1 h oxycodone IVSA interval was sufficient to normalize these elevated reward thresholds, as was, paradoxically, a 60 h weekend abstinence. The increase in ICSS thresholds was attenuated in a group administered the long-acting kappa opioid antagonist norBNI prior to IVSA training.Conclusions and ImplicationsChanges in brain reward function during escalation of oxycodone selfadministration is driven by an interplay between kappa opioid receptor-mediated negative affective state associated with escalated oxycodone intake and dynamic restoration of brain reward status during longer periods of abstinence.

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