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Journal of Integrative Neuroscience  2020, Vol. 19 Issue (1): 11-19    DOI: 10.31083/j.jin.2020.01.1190
Original Research Previous articles | Next articles
Activation of cannabinoid receptor type 1 impairs spatial and temporal aspects of episodic-like memories in rats
Ko-En Chiang1, Yi-Tse Hsiao1, *()
1Department of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan
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The endocannabinoid system modulates many brain functions, including episodic memories, which contain memories of time and places. Most studies have focused on the involvement of the endocannabinoid system in spatial memory; however, its role in temporal memory is not well understood. Few studies have tested whether the unilateral endocannabinoid system is sufficient to modulate memory retrieval. Here, we tested whether type 1 cannabinoid receptors in the right hippocampal cornu ammonis area 1 region are enough to modulate the retrieval of episodic memories, specifically their spatial and temporal components. Because rats have innate preferences for displaced or old familiar objects, we changed the locations of “old familiar” and “recent familiar” objects in an open field and measured the rats’ exploration times to evaluate spatial and temporal memory. To address the influence of the type 1 cannabinoid receptors on the retrieval of episodic-like memories, two doses of arachidonylcyclopropylamide, a selective type 1 cannabinoid receptor agonist, were infused into the cornu ammonis area 1 of rats ten minutes before the discrimination trials. We observed that rats injected with a low dose of arachidonylcyclopropylamide spent less time investigating displaced objects, suggesting spatial memory impairment, whereas those receiving a high dose explored old familiar objects less frequently, suggesting temporal memory impairment. This indicates that unilateral activation of type 1 cannabinoid receptors in the cornu ammonis area 1 impairs the spatial and temporal aspects of episodic memories. This research mimics the influence of marijuana intoxication effects in humans, such as spatial and temporal disintegration.

Key words:  Endocannabinoid system      marijuana intoxication      CA1 hippocampus      episodic memory      temporal disintegration      spatial memory     
Submitted:  19 September 2019      Accepted:  07 February 2020      Published:  30 March 2020     
106-2320-B-002-002-MY2/Ministry of Science and Technology
108-2320-B-002-074/Ministry of Science and Technology
*Corresponding Author(s):  Yi-Tse Hsiao     E-mail:

Cite this article: 

Ko-En Chiang, Yi-Tse Hsiao. Activation of cannabinoid receptor type 1 impairs spatial and temporal aspects of episodic-like memories in rats. Journal of Integrative Neuroscience, 2020, 19(1): 11-19.

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Figure 1.  Photograph of a histologically processed section depicting the injection site and a schematic drawing of the coordinates for the objects. (A) The microinjection cannula was aimed at the dorsal CA1. (B) The objects were placed in the northwest (NW), north-center (NC), northeast (NE), southwest (SW), south-center (SC), and southeast (SE) sections depending on which trial was being executed. The rats always faced north at the beginning of each trial.

Figure 2.  Schematic drawing of the protocols of the three-trial object exploration task. The subjects had two encoding trials with different objects placed in different locations. Ten minutes before the discrimination trial, a CB1 receptor agonist or PFS was infused into CA1. One week later, a similar protocol was conducted, but with different object sets. Moreover, if the subjects received PFS before, they were alternately injected with the CB1 receptor agonist and vice versa. The walls of the open field and their visual cues used in the control sessions were different from those in the ACPA sessions.

Figure 3.  Exploration times during the discrimination trials. The top panel is an illustration showing which exploration times were compared (exploration times of the black objects were calculated). The time the rats spent exploring the old familiar and recent familiar objects demonstrated their ability to discriminate object sequences that require memories of “what” and “when” (A and B). Rats require memories of “what” and “where” to differentiate displaced and stationary objects (C and D). (A) and (C) depict the results for the low-dose group and (B) and (D) depict those of the high-dose group. The bars depict the means ± SEMs. * represents a significant difference, P < 0.05.

Table 1  Summary table. Summary of the rats’ preferences for objects after each manipulation.
Recent or old familiar objects
Stationary or displaced objects
PFS (low-dose group) Old familiar objects Displaced objects
ACPA (low-dose group) Old familiar objects Equal
PFS (high-dose group) Old familiar objects Displaced objects
ACPA (high-dose group) Equal Displaced objects
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