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In 2016, World Health Organization [WHO] reported that worldwide cannabis is the most consumed illicit drug, however, evidence regarding its psychological impacts are inconclusive (Cohen et al., 2019; Hammond et al., 2020; Korn et al., 2018; Metrik et al., 2011; Musardo & Bellone, 2018; Volkow et al., 2017). This reveals the relevance of studying the impact of cannabis on psychological processes modulated by the endocannabinoid system, such as reward and Anxiety, where THC (Δ9-tetrahydrocannabinol, this drug main psychoactive component) exerts its effect (Parsons & Hurd, 2015; Ruehle et al., 2012). Particularly, studies about reward and cannabis (or pure THC) have focused on reward as a reinforcer, and in animal models, most of the related literature is based on the use of artificial rewards (i.e., the same or other drugs; Bhattacharyya et al., 2012; Braida et al., 2004; Cadoni et al., 2015; Kubilius et al., 2018; Lawn et al., 2016; Spano et al., 2007; Van Hell et al., 2012). In contrast, fewer studies have incorporated a multidimensional concept of reward (evaluating its motivational, hedonic, and associative components), autoshaping behavior (sign tracking), and the use of natural rewards (i.e., social interaction and food), corresponding to fundamental elements for the subject's survival (Anselme et al, 2013; Bai et al., 2014; Berridge & Robinson 1998; Delamater et al., 2018; Jiang et al., 2015; Lesser et al; 2017; Smith et al., 2011). Regarding anxiety and cannabis (or pure THC), literature reveal conflicts between this drug consumption and its anxiogenic or anxiolytic effects, varying among other factors, the dose of the drug and exposure time (Bhattacharyya et al., 2009; Fokos & Panagis, 2010; Fusar-Poli et al., 2009; Kubilius et al., 2018; Metrik et al., 2011). Additionally, several investigations have posited a relationship between anxiety and reward (Booth & Hasking, 2009; Hahn et al., 2017; Silk et al., 2012), however, studies analyzing this correlation integrating THC consumption are scarce. Determining the consequences of the consumption of this drug on anxiety and reward becomes relevant at two levels: recent cannabis exposure (RCE, after drug delivery or consumption), in which the cannabis literature is mostly focused, and prenatal cannabis exposure (PCE), which has become relevant due to the increase of cannabis consumption by pregnant women, generating a fetal exposure of the drug (Hammond et al., 2020; Hurd, 2020; Weisbeck et al., 2020; Westfall et al., 2006). Given this background, we will explore the effects of RCE and PCE on anxiety and reward, using an animal model. The general aim of this study will be to determine the consequences of Prenatal and recent exposure to cannabis over anxiety and reward. For this, we contemplate the use of 18 adults (as parental trios) and 96 descendants (offspring from parental trio) of Sprague Dawley rats of both sexes, distributed equally among 5 replications and one pilot. Rat offspring from a mother exposed to 10mg of cannabis (composing the PCE+ group) and the offspring of a mother exposed to vehicle solution (composing a PCE- group) will be subdivided and exposed to cannabis (RCE+) or vehicle (RCE-) prior to testing, giving place to 4 experimental groups (n=4). The experimental task will be performed within postnatal day 28-60. In each replication, the same animals will be used in both anxiety and reward tasks. For anxiety measurements, we will perform an elevated plus maze and a free exploratory behavior task. Also, we will evaluate fecal corticosterone level as an anxiety physiological measurement. Then, for reward measurements we will: A) use an effort and a tickle task to evaluate reward's motivational component, B) using the same tickle task and a sucrose preference task we will evaluate reward's hedonic component, and C) using a conditioned place preference and a magazine approach task we will evaluate rewards associative component. This study will be implemented considering three project components expressed under three specific objectives and eleven subspecific objectives according to each variable of interest: General aim: We will determine the effects of prenatal and recent cannabis exposure on anxiety and reward Study Component 1: PCE and RCE on Anxiety Specific Objective 1 (SO1): We will evaluate the effects of PCE and RCE on anxiety. Sub-specific objective 1.A (SSO1.A): We will determine the effects of PCE and RCE on anxiety using an elevated plus maze tasks Sub-specific objective 1.B (SSO1.B): We will determine the effects of PCE and RCE on anxiety using a free exploratory behavior task Sub-specific objective 1.C (SSO1.C): We will determine the effects of PCE and RCE on fecal corticosterone levels. Study Component 2: PCE and RCE on Reward Components Specific Objective 2 (SO2): We will evaluate the effects of PCE and RCE on the motivational, hedonic, and associative components of reward. Motivation: Sub-specific objective 2.A (SSO2.A): We will determine the effects of PCE and RCE on reward motivation using a tickling task. Sub-specific objective 2.B (SSO2.B): We will determine the effects of PCE and RCE on reward motivation using an effort task. Hedonic: Sub-specific objective 2.C (SSO2.C): We will determine the effects of PCE and RCE on reward hedonic impact using a tickling task. Sub-specific objective 2.D (SSO2.D): We will determine the effects of PCE and RCE on reward hedonic impact using a sucrose preference task. Associative: Sub-specific objective 2.D (SSO2.E): We will determine the effects of PCE and RCE on reward preference learning using a conditional place preference task. Sub-specific objective 2.F (SSO2.F): We will determine the effects of PCE and RCE on reward associative learning using a magazine approach task. Sub-specific objective 2.G (SSO2.G): We will determine the effects of PCE and RCE on reward autoshaped behavior using a magazine approach task. Study Component 3: PCE and RCE on Anxiety and Reward Specific Objective 3 (SO3): We will evaluate the effect of PCE and RCE on anxiety and reward, as well as anxiety moderation effects over reward. Sub-specific objective (SSO3): We will determine, using path analysis, the effects of PCE and RCE on anxiety and reward, together with anxiety moderation over these effects. |
