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Effects of chronic THC in adolescence on rat play behaviours

Citation

Keeley, Robin; Himmler, Stephanie; Pellis, Sergio; McDonald, Robert (2021), Effects of chronic THC in adolescence on rat play behaviours , Dryad, Dataset, https://doi.org/10.5061/dryad.v9s4mw6x4

Abstract

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. This study contributes to understanding the long-term ramifications of adolescent THC exposure on healthy brain development. Disruptions in social behaviour during this period could have long-term consequences on adult brain and behaviour, and the interaction between the pharmacological effects of THC and the subsequent effects of decreased sociality should be considered.

Methods

A total of 48 Long–Evans rats (24 females and 24 males; RRID: RGD_18337282) were used. Following weaning, male and female rats were randomly assigned and counterbalanced to their experimental groups: comparison control (CC; N=6), control (CON; N=6) vehicle (VEH; N=6) or THC (N=6) so that each quadrad included one same-sex partner subject from each experimental group. Treatment began following puberty onset using the external changes to the genitalia, which reliably signal the onset of puberty. THC (in 1:1:18 solution of ethanol: cremaphor:saline) was administered i.p. at a dose of 5 mg/kg once a day starting on the day of puberty onset for 14 days. VEH groups were given a vehicle injection once a day for 14 days. Play behaviour consisted of placing two play partners in large, clear Plexiglas arena filled to a depth of ~1–2 cm with Betacob bedding. Play was recorded for 10 min in the dark using a video camera with night-shot capacity. Play behaviour was assessed at least seven days following the onset of the injection period ~1 hour after treatment. 24 hours before play trials partners were separated and housed individually. Within a quadrad, all treatment rats (CON, VEH and THC) were paired with the CC rat for play bouts. The order of play bouts with the CC was counterbalanced. The frequency of nape attacks (in which the snout of one partner moves towards the nape of the other), the likelihood of the partner receiving a nape attack defending itself to avoid contact and if it did defend itself, and the tactics used to do so were scored. The total frequency of nape attacks per 10 min were scored and analyzed, but as defense is contingent on attack, the frequency of defense was expressed as a percentage of attacks received, and the types of defense were expressed as a percentage of defended attacks. Defense can involve either evasion (the head and neck are turned away from the attacker) or facing defense (the defender turns to face the attacker). The percentage of evasion provides a measure of attempts by rats to avoid playful contact. In facing defense, the rats can either remain standing or roll over to supine, with the percentage of the latter providing a measure of the rat’s motivation to gain and maintain close body contact. A common configuration resulting from attack and defense in the juvenile period is for one rat to lie on its back and the partner to stand over it (i.e., a pin). As the absolute number of pins per trial was also scored to provide insight into the pattern of interaction.

Usage Notes

The readme file contains an explanation of each of the variables in the dataset. Information on how the behaviours were scored can be found in the manuscript referenced above.  

Funding

Natural Sciences and Engineering Research Council of Canada, Award: RGPIN-2015-06347

Natural Sciences and Engineering Research Council of Canada, Award: RGPIN-2020-06929