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Domi, E., Xu, L., Toivainen Eloff, S., Wiskerke, J., Coppola, A., Holm, L., . . . Heilig, M. (2023). Activation of GABA(B) receptors in central amygdala attenuates activity of PKC delta plus neurons and suppresses punishment-resistant alcohol self-administration in rats. Neuropsychopharmacology, 48, 1386-1395
Open this publication in new window or tab >>Activation of GABA(B) receptors in central amygdala attenuates activity of PKC delta plus neurons and suppresses punishment-resistant alcohol self-administration in rats
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2023 (English)In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 48, p. 1386-1395Article in journal (Refereed) Published
Abstract [en]

Alcohol use despite negative consequences is a core phenomenon of alcohol addiction. We recently used alcohol self-administration that is resistant to footshock punishment as a model of this behavior, and found that activity of PKC delta + GABAergic neurons in the central amygdala (CeA) is a determinant of individual susceptibility for punishment resistance. In the present study, we examined whether activation of GABA(B) receptors in CeA can attenuate the activity of PKC delta + neurons in this region, and whether this will result in suppression of punishment- resistant alcohol self-administration in the minority of rats that show this behavior. Systemic administration of the clinically approved GABA(B) agonist baclofen (1 and 3 mg/kg) dose- dependently reduced punishment-resistant alcohol self-administration. Bilateral microinjections of baclofen into CeA (64 ng in 0.3 mu l/side) reduced the activity of PKC delta + neurons, as measured by Fos expression. This manipulation also selectively suppressed punished alcohol self-administration in punishment-resistant rats. Expression analysis indicated that virtually all CeA PKC delta + neurons express the GABA(B) receptor. Using in vitro electrophysiology, we found that baclofen induced hyperpolarization of CeA neurons, reducing their firing rate in response to depolarizing current injections. Together, our findings provide a potential mechanism that contributes to the clinical efficacy of baclofen in alcohol addiction. Therapeutic use of baclofen itself is limited by problems of tolerance and need for dose escalation. Our findings support a mechanistic rationale for developing novel, improved alcohol addiction medications that target GABA(B) receptors, and that lack these limitations, such as e.g., GABA(B) positive allosteric modulators (PAM:s).

Place, publisher, year, edition, pages
SPRINGERNATURE, 2023
National Category
Neurosciences
Identifiers
urn:nbn:se:liu:diva-191971 (URN)10.1038/s41386-023-01543-1 (DOI)000926088900001 ()36739350 (PubMedID)
Available from: 2023-02-28 Created: 2023-02-28 Last updated: 2024-03-05Bibliographically approved
Pieslinger, J., Wiskerke, J. & Igelström, K. (2022). Contributions of face processing, social anhedonia and mentalizing to the expression of social autistic-like traits. Frontiers in Behavioral Neuroscience, 16, Article ID 1046097.
Open this publication in new window or tab >>Contributions of face processing, social anhedonia and mentalizing to the expression of social autistic-like traits
2022 (English)In: Frontiers in Behavioral Neuroscience, E-ISSN 1662-5153, Vol. 16, article id 1046097Article in journal (Refereed) Published
Abstract [en]

Quantitative autistic-like traits (QATs) are a constellation of traits that mirror those of clinical autism and are thought to share the same mechanisms as the condition. There is great interest in identifying the genetic and neurobiological basis of QATs, but progress is hindered by the composite nature of these clinically based constructs. Social QATs are defined according to the diagnostic criteria for autism, comprising multiple potential neural mechanisms that may contribute to varying degrees. The objective of this study was to decompose social QATs into more specific constructs, in line with the Research Domain Criteria (RDoC). We chose constructs with trait-like properties and known or suggested significance for autistic social function: 1) social anhedonia, 2) prosopagnosia (face blindness), and 3) mentalizing (attributing mental states to images of eyes). We hypothesized that these constructs may all contribute to observed variance in social QATs. We recruited 148 adults with a broad range of QATs (mean age 37.9 years, range 18–69; 50% female; 5.4% autistic) to an experimental behavioral study conducted online. We estimated social QATs using the social factor of the Comprehensive Autistic Traits Inventory. We used the Oxford Face Matching Task and the Reading the Mind in the Eyes Test to measure face matching ability and mentalizing, respectively. Social anhedonia traits were measured with the Anticipatory and Consummatory Interpersonal Pleasure Scale, and prosopagnosic traits with the 20-item Prosopagnosia Index. A combination of frequentist and Bayesian statistics was used to test the social constructs as predictors of social QATs. We found that social anhedonic traits, prosopagnosic traits, and face matching performance were likely predictors of social QATs, whereas mentalizing showed limited contribution. The findings support prosopagnosic and anhedonic traits, but not mentalizing deficits, as dimensional predictors of individual differences in social function across the autistic spectrum. Further, the study strongly suggest that social reward systems and face processing networks play significant and independent roles in autistic-like social function.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2022
National Category
Neurosciences
Identifiers
urn:nbn:se:liu:diva-190420 (URN)10.3389/fnbeh.2022.1046097 (DOI)000907694500001 ()36620857 (PubMedID)
Funder
Swedish Research Council
Note

Funding: Swedish Research Council;  [2018-02131]

Available from: 2022-12-07 Created: 2022-12-07 Last updated: 2024-07-04Bibliographically approved
Wiskerke, J., Stern, H. & Igelström, K. (2018). Camouflaging of repetitive movements in autistic female and transgender adults. , Article ID 412619.
Open this publication in new window or tab >>Camouflaging of repetitive movements in autistic female and transgender adults
2018 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Repetitive movements (RMs), colloquially called “stimming” among adult autistic people and “motor stereotypies” among scientists, are common in autism. These behaviors fall under the domain of restricted and repetitive behaviors in the current edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). RMs can be socially disruptive or cause self-harm, but can also be experienced as cognitively or emotionally helpful and even enjoyable. Overt RMs are less common in females than in males, which could contribute to clinical difficulties in detecting their autism. In the social domain, autistic people with intact intelligence can often mask their social difficulties through various compensation strategies, and females appear especially skilled at it. Subjective report from verbally able adults may be useful as a first step in detecting potential camouflaging of RMs, and to provide a foundation for further studies. We founded an Internet-based outreach platform that became particularly successful in reaching female and transgender individuals. We recruited 342 individuals to an anonymous online questionnaire, collected data about self-reported RMs and probed for potential camouflaging. The cohort comprised 56% formally diagnosed participants and 44% who self-identified as autistic, and 17% of all participants reported non-cisgender identity. Thus, in addition to diagnosed women, we reached two populations that would normally be excluded from autism studies: transgender and undiagnosed participants. We found high rates of RMs in both diagnosed and self-identifying participants, and a striking prevalence of camouflaging. We suggest that camouflaging of RMs may contribute to underdiagnosis of autism, at least in females and transgender people, and that further studies on this topic are exceptionally important.

National Category
Psychology (excluding Applied Psychology)
Identifiers
urn:nbn:se:liu:diva-169919 (URN)10.1101/412619 (DOI)
Note

This is an unpublished preprint posted on bioRxiv (the preptint server for biology). The preprint has not been formally peer-reviewed.

Available from: 2020-09-24 Created: 2020-09-24 Last updated: 2022-04-26Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-5029-341x

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