Altering endocannabinoid neurotransmission at critical developmental ages: Impact on rodent emotionality and cognitive performance

Department of Biology, University "Roma Tre" Rome, Italy.
Frontiers in Behavioral Neuroscience (Impact Factor: 3.27). 01/2012; 6:2. DOI: 10.3389/fnbeh.2012.00002
Source: PubMed


THE ENDOCANNABINOID SYSTEM SHOWS FUNCTIONAL ACTIVITY FROM EARLY STAGES OF BRAIN DEVELOPMENT: it plays an important role in fundamental developmental processes such as cell proliferation, migration, and differentiation, thus shaping brain organization during pre- and postnatal life. Cannabis sativa preparations are among the illicit drugs most commonly used by young people, including pregnant women. The developing brain can be therefore exposed to cannabis preparations during two critical periods: first, in offspring of cannabis-using mothers through perinatal and/or prenatal exposure; second, in adolescent cannabis users during neural maturation. In the last decade, it has become clear that the endocannabinoid system critically modulates memory processing and emotional responses. Therefore, it is well possible that developmental exposure to cannabinoid compounds induces enduring changes in behaviors and neural processes belonging to the cognitive and emotional domains. We address this issue by focusing on rodent studies, in order to provide a framework for understanding the impact of cannabinoid exposure on the developing brain.

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Available from: Viviana Trezza, Mar 19, 2014
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    • "It is known since ancient times that exposure to cannabisderived drugs produces a wide range of effects on emotionality in humans (Zanettini et al., 2011). Upon discovery and characterization of the endocannabinoid system, it has become clear that these effects are related to the abundance of cannabinoid receptors in brain areas involved in emotional responses, where endocannabinoids influence the activity of neurotransmitter systems involved in emotion and motivation (Haller et al., 2004; Millan, 2003; Trezza et al., 2012a). "
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    ABSTRACT: Genetic and environmental factors play an important role in the cannabinoid modulation of motivation and emotion. Therefore, the aim of the present study was to test whether anandamide modulation of social behavior is strain- and context-dependent. We tested the effects of the anandamide hydrolysis inhibitor URB597 on social behavior and 50-kHz ultrasonic vocalizations (USVs) in adolescent and adult Wistar and Sprague–Dawley rats tested in different emotionally arousing conditions (familiarity/unfamiliarity to the test cage, low/high light). Under all experimental conditions, adolescent and adult Sprague–Dawley rats displayed higher levels of social behavior and emitted more 50-kHz USVs than Wistar rats. URB597 enhanced social play behavior in adolescent Wistar rats under all experimental conditions. However, URB597 only increased social interaction in adult Wistar rats under unfamiliar/high light conditions. URB597 did not affect adolescent social play behavior and adult social interaction in Sprague–Dawley rats under any experimental condition. Moreover, URB597 increased the USVs emitted during social interaction by adolescent Wistar and adult Sprague–Dawley rats tested under familiar/high light and unfamiliar/high light, respectively. These results show that anandamide has distinct roles in adolescent and adult social behaviors. Anandamide modulation of adolescent social play behavior is strain- but not context-dependent. Conversely, anandamide modulation of adult social behavior and USV emission depends upon both strain and experimental context. Furthermore, these results confirm that profound behavioral differences exist between Wistar and Sprague–Dawley rats, which may explain the sometimes contradictory effects of cannabinoid drugs on emotionality in different strains of rodents.
    Full-text · Article · Aug 2014 · European Neuropsychopharmacology
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    • "The hippocampus is the most relevant brain structure for spatial learning (Moser et al., 1993; Pearce et al., 1998; Richmond et al., 1999; Talpos et al., 2008) and it expresses high levels of CB1R that peak during adolescence (Soderstrom and Gilbert, 2013). Administration of Δ 9 -tetrahydrocannabinol (THC) reduces neurotransmitter release, alters the activity of several receptor systems and perturbs second messenger signalling in the hippocampus (Fishbein et al., 2012; Long et al., 2013; Mateos et al., 2011; Trezza et al., 2012). Perhaps unsurprisingly, cannabinoids disrupt long-term potentiation (LTP) in hippocampal neurons (Collins et al., 1995; Misner and Sullivan, 1999; Terranova et al., 1995). "
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    ABSTRACT: Cannabis is the most widely used illicit drug, and disruption of learning and memory are commonly reported consequences of cannabis use. We have previously demonstrated a spatial learning impairment by ∆(9)-tetrahydrocannabinol (THC) in adolescent Sprague-Dawley rats (Steel, Miller, Sim & Day, 2011). The molecular mechanisms underlying behavioural impairment by cannabis remain poorly understood, although the importance of adaptive changes in neuroplasticity (synaptic number and strength) and neurogenesis during learning are accepted. Here we aimed to identify any effects of THC on the early induction of these adaptive processes supporting learning, so we conducted our analyses at the mid-training point of our previous study. Both untrained and trained (15 days of training) adolescent (P28 - P42) Sprague-Dawley rats were treated daily with THC (6mg/kg i.p.) or its vehicle, and changes in the levels of markers of hippocampal neuroplasticity (CB1R, PSD95, synapsin-I, synapsin-III) and neurogenesis (Ki67, DCX, PSA-NCAM, BrdU labelling) by training were measured. Training of control animals, but not THC-treated animals increased neuroplasticity marker levels. However training of THC-treated animals, but not control animals reduced immature neuronal marker levels. Levels of hippocampal proliferation, and survival of the BrdU-labelled progeny of these divisions were unaffected by THC in trained and untrained animals. These data show a smaller neuroplastic response, and a reduction of new-born neuronal levels not attributable to effects on proliferation or survival by THC-treatment during training. Importantly no effects of THC were seen in the absence of training, indicating that these effects represent specific impairments by THC on training-induced responses.
    Full-text · Article · Jan 2014 · Brain research
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    • "Moreover, our findings are in accordance with the general assumption that the capability to recognize a new setting of the environment is important for the species survival, but the impact of the object novelty is more salient than a spatial rearrangement with the same objects (Mumby et al., 2002). Extensive evidence demonstrates that the endocannabinoid system is a crucial regulator of emotionality and cognition (Marsicano et al., 2002; Laviolette and Grace, 2006a,b; Campolongo et al., 2009a,b; Mackowiak et al., 2009; Abush and Akirav, 2010; Akirav, 2011; Trezza et al., 2012). Although the neurobiological mechanisms underlying cannabinoid manipulation of emotional and cognitive functions have not yet been completely elucidated, previous evidence demonstrates that the anxiolytic effects induced by pharmacological enhancement of endocannabinoid tone strongly depend on the emotional state at the time of testing (Patel and Hillard, 2006) and that these effects are modulated by the level of emotional reactivity induced by high or low aversive experimental conditions (Haller et al., 2009). "
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    ABSTRACT: Cannabinoid compounds may influence both emotional and cognitive processes depending on the level of environmental aversiveness at the time of drug administration. However, the mechanisms responsible for these responses remain to be elucidated. The present experiments investigated the effects induced by the endocannabinoid transport inhibitor AM404 (0.5-5 mg/kg, i.p.) on both emotional and cognitive performances of rats tested in a Spatial Open Field task and subjected to different experimental settings, named High Arousal (HA) and Low Arousal (LA) conditions. The two different experimental conditions influenced emotional reactivity independently of drug administration. Indeed, vehicle-treated rats exposed to the LA condition spent more time in the center of the arena than vehicle-treated rats exposed to the HA context. Conversely, the different arousal conditions did not affect the cognitive performances of vehicle-treated animals such as the capability to discriminate a spatial displacement of the objects or an object substitution. AM404 administration did not alter locomotor activity or emotional behavior of animals exposed to both environmental conditions. Interestingly, AM404 administration influenced the cognitive parameters depending on the level of emotional arousal: it impaired the capability of rats exposed to the HA condition to recognize a novel object while it did not induce any impairing effect in rats exposed to the LA condition. These findings suggest that drugs enhancing endocannabinoid signaling induce different effects on recognition memory performance depending on the level of emotional arousal induced by the environmental conditions.
    Full-text · Article · Mar 2012 · Frontiers in Behavioral Neuroscience
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