Chronic exposure to ∆9-tetrahydrocannabinol in adolescence decreases social play behaviours

Background: Cannabis use remains a major public health concern, and its use typically begins in adolescence. Chronic administration of ∆9-tetrahydrocannabinol (THC), the main psychoactive compound in cannabis, during adolescence can produce deficits in adult learning and memory, stress reactivity and anxiety. One possible mechanism behind the disruptions in adulthood from adolescent exposure to THC includes changes in social behaviours, such as social play, which has been shown to be critical to socio-cognitive development. Methods: Here, using an established animal model of adolescent THC exposure in male and female Long–Evans rats, we explored the effects of THC on play behaviour during the chronic administration period. Following puberty onset, as indicated by external changes to the genitalia, THC (5mg/kg) was administered for 14 days. Play behaviour was assessed seven days following the onset of the injection period at approximately 1 hour post treatment. The frequency of nape attacks, the likelihood and tactics of defensive behaviour, and pins were scored and analyzed. Results: THC exposure decreased playfulness in adolescent rats including the number of attacks, likelihood of defense and pins compared to control and vehicle treated rats. Conclusion: This suggests that THC suppresses both the attack and defense components of social play. This is an important finding because there is evidence that attack and defense may be mediated by different mechanisms. Furthermore, the effect of THC exposure decreasing playfulness occurred similarly in males and females.

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Acute and constitutive increases in central serotonin levels reduce social play behaviour in peri-adolescent rats

Psychopharmacology ◽

10.1007/s00213-007-0895-8 ◽

2007 ◽

Vol 195 (2) ◽

pp. 175-182 ◽

Cited By ~ 67

Author(s):

Judith R. Homberg ◽

Olga J. G. Schiepers ◽

Anton N. M. Schoffelmeer ◽

Edwin Cuppen ◽

Louk J. M. J. Vanderschuren

Keyword(s):

Social Play ◽

Play Behaviour ◽

Adolescent Rats

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P.2.27 Effects of nicotine and ethanol on social play behaviour in adolescent rats

European Neuropsychopharmacology ◽

10.1016/s0924-977x(09)70065-3 ◽

2009 ◽

Vol 19 ◽

pp. S55-S56

Author(s):

V. Trezza ◽

P.J.J. Baarendse ◽

L.J.M.L. Vanderschuren

Keyword(s):

Social Play ◽

Play Behaviour ◽

Adolescent Rats

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The Effect of Maternal Immune Activation on Social Play-Induced Ultrasonic Vocalization in Rats

Brain Sciences ◽

10.3390/brainsci11030344 ◽

2021 ◽

Vol 11 (3) ◽

pp. 344

Author(s):

Kinga Gzielo ◽

Agnieszka Potasiewicz ◽

Ewa Litwa ◽

Diana Piotrowska ◽

Piotr Popik ◽

...

Keyword(s):

Immune Activation ◽

Social Play ◽

Autism Spectrum ◽

Repetitive Behaviors ◽

Male Rats ◽

Poly I:C ◽

Maternal Immune Activation ◽

Increased Risk ◽

Adolescent Rats ◽

The Impact

Prenatal maternal infection is associated with an increased risk of various neurodevelopmental disorders, including autism spectrum disorders (ASD). Maternal immune activation (MIA) can be experimentally induced by prenatal administration of polyinosinic:polycytidylic acid (poly I:C), a synthetic viral-like double-stranded RNA. Although this MIA model is adopted in many studies, social and communicative deficits, included in the first diagnostic criterion of ASD, are poorly described in the offspring of poly(I:C)-exposed dams. This study aimed to characterize the impact of prenatal poly(I:C) exposure on socio-communicative behaviors in adolescent rats. For this purpose, social play behavior was assessed in both males and females. We also analyzed quantitative and structural changes in ultrasonic vocalizations (USVs) emitted by rats during the play test. Deficits of social play behaviors were evident only in male rats. Males also emitted a significantly decreased number of USVs during social encounters. Prenatal poly(I:C) exposure also affected acoustic call parameters, as reflected by the increased peak frequencies. Additionally, repetitive behaviors were demonstrated in autistic-like animals regardless of sex. This study demonstrates that prenatal poly(I:C) exposure impairs socio-communicative functioning in adolescent rats. USVs may be a useful tool for identifying early autistic-like abnormalities.

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Long-Term Consequences of Adolescent Exposure to THC-Rich/CBD-Poor and CBD-Rich/THC-Poor Combinations: A Comparison with Pure THC Treatment in Female Rats

International Journal of Molecular Sciences ◽

10.3390/ijms22168899 ◽

2021 ◽

Vol 22 (16) ◽

pp. 8899

Author(s):

Marina Gabaglio ◽

Erica Zamberletti ◽

Cristina Manenti ◽

Daniela Parolaro ◽

Tiziana Rubino

Keyword(s):

Adverse Effects ◽

Chronic Administration ◽

Female Rats ◽

Acid Decarboxylase ◽

Long Term Effects ◽

Gabaergic Neurotransmission ◽

Long Term Consequences ◽

Adolescent Exposure ◽

Long Term Adverse Effects

Cannabis is the most-used recreational drug worldwide, with a high prevalence of use among adolescents. In animal models, long-term adverse effects were reported following chronic adolescent exposure to the main psychotomimetic component of the plant, delta-9-tetrahydrocannabinol (THC). However, these studies investigated the effects of pure THC, without taking into account other cannabinoids present in the cannabis plant. Interestingly, cannabidiol (CBD) content seems to mitigate some of the side effects of THC, at least in adult animals. Thus, in female rats, we evaluated the long-term consequences of a co-administration of THC and CBD at a 3:1 ratio, chosen based on the analysis of recently confiscated illegal cannabis samples in Europe. CBD content is able to mitigate some of the long-term behavioral alterations induced by adolescent THC exposure as well as long-term changes in CB1 receptor and microglia activation in the prefrontal cortex (PFC). We also investigated, for the first time, possible long-term effects of chronic administration of a THC/CBD combination reminiscent of “light cannabis” (CBD:THC in a 33:1 ratio; total THC 0.3%). Repeated administration of this CBD:THC combination has long-term adverse effects on cognition and leads to anhedonia. Concomitantly, it boosts Glutamic Acid Decarboxylase-67 (GAD67) levels in the PFC, suggesting a possible lasting effect on GABAergic neurotransmission.

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Puberty Onset in Males and Females Fed a High Fat Diet

Experimental Biology and Medicine ◽

10.3181/00379727-166-41062 ◽

1981 ◽

Vol 166 (2) ◽

pp. 294-296 ◽

Cited By ~ 6

Author(s):

J. A. Ramaley

Keyword(s):

High Fat Diet ◽

High Fat ◽

Males And Females ◽

Puberty Onset

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Abstract 034: Characterization of A Novel Maternally Restricted Pro-angiogenic Therapeutic for Preeclampsia

Hypertension ◽

10.1161/hyp.68.suppl_1.034 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

William H Stewart ◽

Eric George ◽

Gene L Bidwell ◽

Heather Chapman ◽

Fakhri Mahdi ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Half Life ◽

Plasma Concentrations ◽

Subcutaneous Administration ◽

Chronic Administration ◽

Health Concern ◽

Pathogenic Factors ◽

Clearance Kinetics

Background: Preeclampsia is a major obstetrical health concern, affecting 5-8% of all pregnancies. Hallmarked by hypertension and endothelial dysfunction the origin of the disease remains obscure, though it is generally accepted that placental insufficiency/ischemia is a central cause. In response, the placenta secretes pathogenic factors, in particular the anti-angiogenic protein sFlt-1. Currently, there is no effective therapy for the management of the preeclampsia patient. We have recently produced a novel synthetic peptide based on placental growth factor (PlGF) which is maternally restricted by fusion to the synthetic carrier elastin like polypeptide (ELP). Here, we describe its in vivo pharmacokinetics and biodistribution. Methods: Fluorescently labeled ELP-PLGF was administered i.v. and blood sampled serially to determine clearance kinetics. Long-term pharmacokinetics and biodistribution was performed after subcutaneous administration of labeled peptide. Measurements were made on serially drawn blood, and in the whole animal by in vivo imaging. Results: ELP-PlGF exhibited markedly more favorable pharmacokinetics than the normal half life of PlGF, with a terminal half-life of ~10 hours as opposed to ~30 minutes for PlGF alone. Chronic administration found highest levels accumulating in placenta and kidney (two favorable targets for preeclampsia) and liver. A single subcutaneous administration at 100mg/kg resulted in sustained therapeutic plasma concentrations for over 10 days. Conclusion: These data demonstrate that ELP-PlGF has favorable pharmacokinetic and biodistribution profiles. Previous data suggest ELP-PlGF directly antagonizes sFlt-1 in culture. Future studies to assess the in vivo effectiveness of ELP-PlGF in managing placental ischemia induced hypertension and endothelial dysfunction are currently in progress. Acknowledgment: This work was supported by NIH grants R0121527 (GLB), T32HL105324 (OCL), P01HL51971, P20GM104357 (EMG), and R00HL116774 (EMG)

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Swinxsbee: A Shared Interactive Play Object to Stimulate Children’s Social Play Behaviour and Physical Exercise

Lecture Notes of the Institute for Computer Sciences, Social Informatics and Telecommunications Engineering - Intelligent Technologies for Interactive Entertainment ◽

10.1007/978-3-642-02315-6_9 ◽

2009 ◽

pp. 90-101 ◽

Cited By ~ 6

Author(s):

Martijn Jansen ◽

Tilde Bekker

Keyword(s):

Physical Exercise ◽

Social Play ◽

Play Behaviour ◽

Interactive Play

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Effect of Morphine Administration on Social and Non-Social Play Behaviour in Calves

Animals ◽

10.3390/ani9020056 ◽

2019 ◽

Vol 9 (2) ◽

pp. 56 ◽

Cited By ~ 1

Author(s):

Mhairi Sutherland ◽

Gemma Worth ◽

Catherine Cameron ◽

Else Verbeek

Keyword(s):

Intravenous Injection ◽

Affective State ◽

Social Play ◽

Play Behaviour ◽

Morphine Administration ◽

Positive Affective State ◽

Arena Test

The objective of this study was to evaluate the effect of morphine on social and non‐socialplay behaviour in calves. Twelve calves experienced four treatments in a cross over 2 × 2 factorialdesign: Calves received an intravenous injection of morphine or saline 10 min prior to being testedindividually or in pairs in an arena for 20 min. Play behaviour was continuously recorded in thearena test. Lying times were recorded in the home pen. Cortisol concentrations were measuredbefore and after testing. In the arena test, calves given morphine tended to perform more social playevents than calves given saline, however, morphine administration had no effect on locomotor play.Calves given morphine spent less time lying than calves given saline during the first 4 h afterreturning to the home pen. Cortisol concentrations were suppressed in calves given morphine.Administration of morphine appeared to increase social play but had no effect on locomotor playin calves. This study highlights the importance of investigating different aspects of play behaviourin animals as some may be more indicative of a positive affective state than others. More studiesinvestigating the effects of morphine on play are needed to confirm the results found in this study.

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Predatory Behaviour and Social Play in Kittens

Behaviour ◽

10.1163/156853981x00013 ◽

1981 ◽

Vol 76 (1-2) ◽

pp. 1-24 ◽

Cited By ~ 31

Author(s):

T.M. Caro

Keyword(s):

Time Course ◽

Social Play ◽

Agonistic Behaviour ◽

Motor Patterns ◽

Predatory Behaviour ◽

Play Behaviour ◽

Before And After ◽

The Relationship

AbstractThis study relates changes in social play of kittens to the development of predatory behaviour. Firstly, it documents the development of predatory motor patterns in young cats between the age of 4 and 12 weeks. Correlations between measures of predatory behaviour were found to break down in the 8 to 12 week period of development. Secondly, it examines the development of social play over the same time course. Correlations between some measures of play were also found to break down between 8 and 12 weeks of age. Finally, measures of social play were correlated with measures of predatory behaviour before and after 8 weeks of age. Some measures of play were found to show increased correlations with predatory behaviour as kittens grew older, others were found to show less association with age. It is concluded that these changes in association between measures of play and predation probably reflect a reorganization of play behaviour. Different play patterns appeared to progressively come under separate types of control as kittens developed. Some patterns were becoming controlled by the same factors as those controlling predatory behaviour, others by those factors that control agonistic behaviour. In addition, the relationship between the timing of the onset of social play and predatory behaviour is examined.

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