doi: 10.3389/fnbeh.2012.00011. eCollection 2012.
The endocannabinoid transport inhibitor AM404 differentially modulates recognition memory in rats depending on environmental aversiveness
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- PMID:22454620
- PMCID: PMC3308193
- DOI: 10.3389/fnbeh.2012.00011
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The endocannabinoid transport inhibitor AM404 differentially modulates recognition memory in rats depending on environmental aversiveness
Patrizia Campolongo et al. Front Behav Neurosci..
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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.
Keywords: cannabinoid system; cognition; emotionality; endocannabinoids; short-term memory.
Figures
Spatial Open-Field procedure. Schematic diagram representing the object configuration in the Spatial Open-Field test:(A) session 1, open field without objects;(B) session 2, habituation session with three stable objects;(C) sessions 3–4, spatial change discrimination sessions where object B displaced object A (session 4);(D) session 5–6, object novelty sessions where object D replaced object C (session 6).
Effects induced by different arousal conditions on locomotor activity and emotional behavior of vehicle-treated rats. Locomotor activity: number of crossing(A) and rearing(B) in session 1. Emotional behavior: time spent in the center of the arena in session 1(C).**P < 0.01. Data are expressed as mean ± SEM. (High Arousal: HAn = 10; Low Arousal: LAn = 15).
Effects induced by different arousal conditions on object investigation and cognitive performances of vehicle-treated rats. Total investigation time of all objects through sessions(A) spatial change discrimination(B) and object novelty discrimination(C).**P < 0.01. Data are expressed as mean ± SEM. (High Arousal: HAn = 10; Low Arousal: LAn = 15).
Effects of AM404 administration on locomotor activity in rats exposed to high arousal (HA) or low arousal (LA) conditions. Number of crossing(A) and rearing(B) of rats exposed to HA or LA conditions(C, D, respectively) in session 1. Data are expressed as mean ± SEM. (HA: vehn = 10, 0.5 mg/kgn = 11, 1 mg/kgn = 10, 5 mg/kgn = 9; LA: vehn = 15, 0.5 mg/kgn = 12, 1 mg/kgn = 14, 5 mg/kgn = 13).
Effects of AM404 administration on emotional behavior in rats exposed to high arousal (HA) or low arousal (LA) conditions. Time spent in the center of the arena by rats exposed to HA(A) or LA conditions(B) in session 1. Data are expressed as mean ± SEM. (HA: vehn = 10, 0.5 mg/kgn = 11, 1 mg/kgn = 10, 5 mg/kgn = 9; LA: vehn = 15, 0.5 mg/kgn = 12, 1 mg/kgn = 14, 5 mg/kgn = 13).
Effects of AM404 administration on object investigation in rats exposed to high arousal (HA) or low arousal (LA) conditions. Total investigation time of all objects by rats exposed to HA(A) or LA(B) conditions through sessions 2–6.*P < 0.05. Data are expressed as mean ± SEM. (HA: vehn = 10, 0.5 mg/kgn = 11, 1 mg/kgn = 10, 5 mg/kgn = 9; LA: vehn = 15, 0.5 mg/kgn = 12, 1 mg/kgn = 14, 5 mg/kgn = 13).
Effects of AM404 administration on spatial change discrimination in rats exposed to high arousal (HA) or low arousal (LA) conditions. Spatial change discrimination index of rats exposed to HA(A) or LA(B) conditions. Tim spent in contact with Displaced (DO) and Non-Displaced (NDO) Objects in session 4 minus the mean time spent in contact with the same object in session 3. A discrimination index was obtained by subtracting the NDO value to DO value. Data are expressed as mean ± SEM. (HA: vehn = 10, 0.5 mg/kgn = 11, 1 mg/kgn = 10, 5 mg/kgn = 9; LA: vehn = 15, 0.5 mg/kgn = 12, 1 mg/kgn = 14, 5 mg/kgn = 13).
Effects of AM404 administration on object novelty discrimination in rats exposed to high arousal (HA) or low arousal (LA) conditions. Object novelty discrimination index of rats exposed to HA(A) or LA(B) conditions. Time spent in contact with Substituted Object (SO, unfamiliar) and Non-Substituted Objects (NSO, familiar) in session 6 minus the mean time spent with objects located in the corresponding position in session 5. A discrimination index was obtained by subtracting the NSO value to SO value.*P < 0.05. Data are expressed as mean ± SEM. (HA: vehn = 10, 0.5 mg/kgn = 11, 1 mg/kgn = 10, 5 mg/kgn = 9; LA: vehn = 15, 0.5 mg/kgn = 12, 1 mg/kgn = 14, 5 mg/kgn = 13).
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