Psychopharmacology

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ISSN / EISSN : 0033-3158 / 1432-2072
Published by: Springer Nature (10.1007)
Total articles ≅ 17,490
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Giulia Margiani, Maria Paola Castelli, Nicholas Pintori, Roberto Frau, Maria Grazia Ennas, Valeria Orrù, Valentina Serra, Edoardo Fiorillo, Paola Fadda, Giovanni Marsicano, et al.
Published: 9 August 2022
Psychopharmacology pp 1-20; https://doi.org/10.1007/s00213-022-06191-9

Abstract:
Rationale: The use of synthetic cannabinoid receptor agonists (SCRAs) is growing among adolescents, posing major medical and psychiatric risks. JWH-018 represents the reference compound of SCRA-containing products. Objectives: This study was performed to evaluate the enduring consequences of adolescent voluntary consumption of JWH-018. Methods: The reinforcing properties of JWH-018 were characterized in male CD1 adolescent mice by intravenous self-administration (IVSA). Afterwards, behavioral, neurochemical, and molecular evaluations were performed at adulthood. Results: Adolescent mice acquired operant behavior (lever pressing, Fixed Ratio 1–3; 7.5 µg/kg/inf); this behavior was specifically directed at obtaining JWH-018 since it increased under Progressive Ratio schedule of reinforcement, and was absent in vehicle mice. JWH-018 IVSA was reduced by pretreatment of the CB1-antagonist/inverse agonist AM251. Adolescent exposure to JWH-018 by IVSA increased, at adulthood, both nestlet shredding and marble burying phenotypes, suggesting long-lasting repetitive/compulsive-like behavioral effects. JWH-018 did not affect risk proclivity in the wire-beam bridge task. In adult brains, there was an increase of ionized calcium binding adaptor molecule 1 (IBA-1) positive cells in the caudate-putamen (CPu) and nucleus accumbens (NAc), along with a decrease of glial fibrillary acidic protein (GFAP) immunoreactivity in the CPu. These glial alterations in adult brains were coupled with an increase of the chemokine RANTES and a decrease of the cytokines IL2 and IL13 in the cortex, and an increase of the chemokine MPC1 in the striatum. Conclusions: This study suggests for the first time that male mice self-administer the prototypical SCRA JWH-018 during adolescence. The adolescent voluntary consumption of JWH-018 leads to long-lasting behavioral and neurochemical aberrations along with glia-mediated inflammatory responses in adult brains.
, Hannes Kettner, Dana Geerts, Sam Gandy, Laura Kartner, Lea Mertens, Christopher Timmermann, Matthew M. Nour, Mendel Kaelen, David Nutt, et al.
Published: 8 August 2022
Psychopharmacology pp 1-23; https://doi.org/10.1007/s00213-022-06187-5

Abstract:
Rationale: A general feeling of disconnection has been associated with mental and emotional suffering. Improvements to a sense of connectedness to self, others and the wider world have been reported by participants in clinical trials of psychedelic therapy. Such accounts have led us to a definition of the psychological construct of ‘connectedness’ as ‘a state of feeling connected to self, others and the wider world’. Existing tools for measuring connectedness have focused on particular aspects of connectedness, such as ‘social connectedness’ or ‘nature connectedness’, which we hypothesise to be different expressions of a common factor of connectedness. Here, we sought to develop a new scale to measure connectedness as a construct with these multiple domains. We hypothesised that (1) our scale would measure three separable subscale factors pertaining to a felt connection to ‘self’, ‘others’ and ‘world’ and (2) improvements in total and subscale WCS scores would correlate with improved mental health outcomes post psychedelic use. Objectives: To validate and test the ‘Watts Connectedness Scale’ (WCS). Methods: Psychometric validation of the WCS was carried out using data from three independent studies. Firstly, we pooled data from two prospective observational online survey studies. The WCS was completed before and after a planned psychedelic experience. The total sample of completers from the online surveys was N = 1226. Exploratory and confirmatory factor analysis were performed, and construct and criterion validity were tested. A third dataset was derived from a double-blind randomised controlled trial (RCT) comparing psilocybin-assisted therapy (n = 27) with 6 weeks of daily escitalopram (n = 25) for major depressive disorder (MDD), where the WCS was completed at baseline and at a 6-week primary endpoint. Results: As hypothesised, factor analysis of all WCS items revealed three main factors with good internal consistency. WCS showed good construct validity. Significant post-psychedelic increases were observed for total connectedness scores (η2 = 0.339, p < 0.0001), as well as on each of its subscales (p < 0.0001). Acute measures of ‘mystical experience’, ‘emotional breakthrough’, and ‘communitas’ correlated positively with post-psychedelic changes in connectedness (r = 0.42, r = 0.38, r = 0.42, respectively, p < 0.0001). In the RCT, psilocybin therapy was associated with greater increases in WCS scores compared with the escitalopram arm (ηp2 = 0.133, p = 0.009). Conclusions: The WCS is a new 3-dimensional index of felt connectedness that may sensitively measure therapeutically relevant psychological changes post-psychedelic use. We believe that the operational definition of connectedness captured by the WCS may have broad relevance in mental health research.
Sahir Hussain, Heidi M. D. Lesscher, Darren J. Day,
Published: 8 August 2022
Psychopharmacology pp 1-15; https://doi.org/10.1007/s00213-022-06195-5

Abstract:
Rationale: Alcohol use disorder (AUD) is shown to have an overall heritability of around 50%. One of the genes associated with AUD is SLC6A4 (solute carrier family 6 member A4) which codes for the serotonin transporter (SERT). The study looked at serotonin dysfunction on ethanol consumption in adolescents and the subsequent intergenerational effects of drinking by using a rat model: SERT+/+ (regular functioning), SERT+/− (50% transporter reduction) and SERT−/− (complete reduction). Objectives: We investigated sex and genotype differences in ethanol consumption in SERT knock-out Wistar rats (F0) followed by studying behaviour in the offspring (F1) of the male drinkers to assess effects of paternal alcohol consumption. Methods: An intermittent access two-bottle choice paradigm (IA2BC) was used to yield ethanol drinking behaviour in F0 adolescent Wistar rats. The highest drinking males were mated to alcohol-naive females and their offspring were compared with controls. Drinking behaviour (IA2BC) and ethanol-induced motor coordination effects (via rotarod) were measured in the F1s. Results: F0 drinking saw no SERT genotype differences in males. However, females consumed higher volumes of ethanol compared to males, with SERT−/− females showing the highest intake. A clearer genotype effect was seen in the F1 animals, with reduction in SERT activity leading to enhanced ethanol intake in both sexes. Importantly, paternal exposure to ethanol significantly reduced the ethanol induced motor side effects in offspring, independent of sex and genotype. Conclusions: These indicate a difference in the way genetic factors may act across sexes and suggest the involvement of epigenetic mechanisms in the intergenerational effects of alcohol.
Dongbin Lyu, Fan Wang, Mengke Zhang, Weichieh Yang, Haijing Huang, Qinte Huang, Chenglin Wu, Nuoshi Qian, Meiti Wang, Huanfei Zhang, et al.
Published: 4 August 2022
Psychopharmacology pp 1-12; https://doi.org/10.1007/s00213-022-06201-w

The publisher has not yet granted permission to display this abstract.
Soghra Borneh Deli, Samira Iman Bonab, , , Mohammadali Hosseinpour Feyzi
Published: 3 August 2022
Psychopharmacology pp 1-14; https://doi.org/10.1007/s00213-022-06199-1

The publisher has not yet granted permission to display this abstract.
Katherine J. Robinson, Nicholas A. Everett, Sarah J. Baracz,
Published: 3 August 2022
Psychopharmacology pp 1-17; https://doi.org/10.1007/s00213-022-06175-9

Abstract:
Introduction: Methamphetamine (METH, “ice”) is a potent and addictive psychostimulant. Abuse of METH perturbs neurotransmitter systems and induces neurotoxicity; however, the neurobiological mechanisms which underlie addiction to METH are not fully understood, limiting the efficacy of available treatments. Here we investigate METH-induced changes to neuronal nitric oxide synthase (nNOS), parvalbumin and calretinin-expressing GABAergic interneuron populations within the nucleus accumbens (NAc), prefrontal cortex (PFC) and orbitofrontal cortex (OFC). We hypothesise that dysfunction or loss of these GABAergic interneuron populations may disrupt the excitatory/inhibitory balance within the brain. Methods: Male Long Evans rats (N = 32) were trained to lever press for intravenous METH or received yoked saline infusions. Following 14 days of behavioural extinction, animals were given a non-contingent injection of saline or METH (1 mg/kg, IP) to examine drug-primed reinstatement to METH-seeking behaviours. Ninety minutes post-IP injection, animals were culled and brain sections were analysed for Fos, nNOS, parvalbumin and calretinin immunoreactivity in eight distinct subregions of the NAc, PFC and OFC. Results: METH exposure differentially affected GABAergic populations, with METH self-administration increasing nNOS immunoreactivity at distinct locations in the prelimbic cortex and decreasing parvalbumin immunoreactivity in the NAc. METH self-administration triggered reduced calretinin immunoreactivity, whilst acute METH administration produced a significant increase in calretinin immunoreactivity. As expected, non-contingent METH-priming treatment increased Fos immunoreactivity in subregions of the NAc and PFC. Conclusion: Here we report that METH exposure in this model may alter the function of GABAergic interneurons in more subtle ways, such as alterations in neuronal firing or synaptic connectivity.
Mackenzie C. Gamble, Byron Chuan, Teresa Gallego-Martin, Micah A. Shelton, Stephanie Puig, Christopher P. O’Donnell,
Published: 1 August 2022
Psychopharmacology pp 1-16; https://doi.org/10.1007/s00213-022-06200-x

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João F. C. Pedrazzi, Frederico R. Ferreira, Danyelle Silva-Amaral, Daniel A. Lima, Jaime E. C. Hallak, Antônio W. Zuardi, Elaine A. Del-Bel, Francisco S. Guimarães, Karla C. M. Costa, Alline C. Campos, et al.
Published: 29 July 2022
Psychopharmacology pp 1-22; https://doi.org/10.1007/s00213-022-06196-4

The publisher has not yet granted permission to display this abstract.
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