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Hippocampal CB(1) receptors mediate the memory impairing effects of Delta(9)-tetrahydrocannabinol.

Wise LE, Thorpe AJ, Lichtman AH - Neuropsychopharmacology (2009)

Bottom Line: The CB(1) receptor antagonist, rimonabant, was delivered into the hippocampus before to a systemic injection of either Delta(9)-THC or the potent cannabinoid analog, CP-55,940.Strikingly, intrahippocampal administration of rimonabant completely attenuated the memory disruptive effects of both cannabinoids in the radial arm maze task, but did not affect other pharmacological properties of cannabinoids, as assessed in the tetrad assay (that is, hypomotility, analgesia, catalepsy, and hypothermia).Infusions of rimonabant just dorsal or ventral to the hippocampus did not prevent Delta(9)-THC-induced memory impairment, indicating that its effects on mnemonic function were regionally selective.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA.

ABSTRACT
It is firmly established that the hippocampus, a brain region implicated in spatial learning, episodic memory, and consolidation, contains a high concentration of CB(1) receptors. Moreover, systemic and intrahippocampal administration of cannabinoid agonists have been shown to impair hippocampal-dependent memory tasks. However, the degree to which CB(1) receptors in the hippocampus play a specific functional role in the memory disruptive effects of marijuana or its primary psychoactive constituent Delta(9)-tetrahydrocannabinol (Delta(9)-THC) is unknown. This study was designed to determine whether hippocampal CB(1) receptors play a functional role in the memory disruptive effects of systemically administered cannabinoids, using the radial arm maze, a well characterized rodent model of working memory. Male Sprague-Dawley rats were implanted with bilateral cannulae aimed at the CA1 region of the dorsal hippocampus. The CB(1) receptor antagonist, rimonabant, was delivered into the hippocampus before to a systemic injection of either Delta(9)-THC or the potent cannabinoid analog, CP-55,940. Strikingly, intrahippocampal administration of rimonabant completely attenuated the memory disruptive effects of both cannabinoids in the radial arm maze task, but did not affect other pharmacological properties of cannabinoids, as assessed in the tetrad assay (that is, hypomotility, analgesia, catalepsy, and hypothermia). Infusions of rimonabant just dorsal or ventral to the hippocampus did not prevent Delta(9)-THC-induced memory impairment, indicating that its effects on mnemonic function were regionally selective. These findings provide compelling evidence in support of the view that hippocampal CB(1) receptors play a necessary role in the memory disruptive effects of marijuana.

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Related in: MedlinePlus

Intracerebral administration of rimonabant (Rim; 0.06 μg/rat) into the dorsal hippocampal does not block the non-mnemonic effects of systemically administered CP-55,940 (CP; 0.15 mg/kg, i.p.), as assessed in the tetrad assay that includes hypomotility (A), antinociception (B), catalepsy (C), and hypothermia (D). * p < 0.05, ** p < 0.01 for each group vs. vehicle-vehicle (V-V) treatment. Results are shown as mean ± SE. n=4-9 rats/group.
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Figure 5: Intracerebral administration of rimonabant (Rim; 0.06 μg/rat) into the dorsal hippocampal does not block the non-mnemonic effects of systemically administered CP-55,940 (CP; 0.15 mg/kg, i.p.), as assessed in the tetrad assay that includes hypomotility (A), antinociception (B), catalepsy (C), and hypothermia (D). * p < 0.05, ** p < 0.01 for each group vs. vehicle-vehicle (V-V) treatment. Results are shown as mean ± SE. n=4-9 rats/group.

Mentions: In the final experiment, we assessed whether intrahippocampal rimonabant administration would attenuate non-mnemonic effects produced by cannabinoids, as assessed in the tetrad assay. As previously reported (Compton, et al 1992), CP-55,940 (0.15 mg/kg, i.p.) produced locomotor suppressive (F (2,16) = 121, p < 0.001; Figure 5A), analgesic (F (2,16) = 6.1, p < 0.05; Figure 5B), cataleptic (Figure 5C), and hypothermic (F (2,16) = 42, p < 0.001; Figure 5D) effects. Intrahippocampal rimonabant (0.06 μg) administration failed to attenuate any of these effects, as indicated by post hoc analyses.


Hippocampal CB(1) receptors mediate the memory impairing effects of Delta(9)-tetrahydrocannabinol.

Wise LE, Thorpe AJ, Lichtman AH - Neuropsychopharmacology (2009)

Intracerebral administration of rimonabant (Rim; 0.06 μg/rat) into the dorsal hippocampal does not block the non-mnemonic effects of systemically administered CP-55,940 (CP; 0.15 mg/kg, i.p.), as assessed in the tetrad assay that includes hypomotility (A), antinociception (B), catalepsy (C), and hypothermia (D). * p < 0.05, ** p < 0.01 for each group vs. vehicle-vehicle (V-V) treatment. Results are shown as mean ± SE. n=4-9 rats/group.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2822461&req=5

Figure 5: Intracerebral administration of rimonabant (Rim; 0.06 μg/rat) into the dorsal hippocampal does not block the non-mnemonic effects of systemically administered CP-55,940 (CP; 0.15 mg/kg, i.p.), as assessed in the tetrad assay that includes hypomotility (A), antinociception (B), catalepsy (C), and hypothermia (D). * p < 0.05, ** p < 0.01 for each group vs. vehicle-vehicle (V-V) treatment. Results are shown as mean ± SE. n=4-9 rats/group.
Mentions: In the final experiment, we assessed whether intrahippocampal rimonabant administration would attenuate non-mnemonic effects produced by cannabinoids, as assessed in the tetrad assay. As previously reported (Compton, et al 1992), CP-55,940 (0.15 mg/kg, i.p.) produced locomotor suppressive (F (2,16) = 121, p < 0.001; Figure 5A), analgesic (F (2,16) = 6.1, p < 0.05; Figure 5B), cataleptic (Figure 5C), and hypothermic (F (2,16) = 42, p < 0.001; Figure 5D) effects. Intrahippocampal rimonabant (0.06 μg) administration failed to attenuate any of these effects, as indicated by post hoc analyses.

Bottom Line: The CB(1) receptor antagonist, rimonabant, was delivered into the hippocampus before to a systemic injection of either Delta(9)-THC or the potent cannabinoid analog, CP-55,940.Strikingly, intrahippocampal administration of rimonabant completely attenuated the memory disruptive effects of both cannabinoids in the radial arm maze task, but did not affect other pharmacological properties of cannabinoids, as assessed in the tetrad assay (that is, hypomotility, analgesia, catalepsy, and hypothermia).Infusions of rimonabant just dorsal or ventral to the hippocampus did not prevent Delta(9)-THC-induced memory impairment, indicating that its effects on mnemonic function were regionally selective.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA.

ABSTRACT
It is firmly established that the hippocampus, a brain region implicated in spatial learning, episodic memory, and consolidation, contains a high concentration of CB(1) receptors. Moreover, systemic and intrahippocampal administration of cannabinoid agonists have been shown to impair hippocampal-dependent memory tasks. However, the degree to which CB(1) receptors in the hippocampus play a specific functional role in the memory disruptive effects of marijuana or its primary psychoactive constituent Delta(9)-tetrahydrocannabinol (Delta(9)-THC) is unknown. This study was designed to determine whether hippocampal CB(1) receptors play a functional role in the memory disruptive effects of systemically administered cannabinoids, using the radial arm maze, a well characterized rodent model of working memory. Male Sprague-Dawley rats were implanted with bilateral cannulae aimed at the CA1 region of the dorsal hippocampus. The CB(1) receptor antagonist, rimonabant, was delivered into the hippocampus before to a systemic injection of either Delta(9)-THC or the potent cannabinoid analog, CP-55,940. Strikingly, intrahippocampal administration of rimonabant completely attenuated the memory disruptive effects of both cannabinoids in the radial arm maze task, but did not affect other pharmacological properties of cannabinoids, as assessed in the tetrad assay (that is, hypomotility, analgesia, catalepsy, and hypothermia). Infusions of rimonabant just dorsal or ventral to the hippocampus did not prevent Delta(9)-THC-induced memory impairment, indicating that its effects on mnemonic function were regionally selective. These findings provide compelling evidence in support of the view that hippocampal CB(1) receptors play a necessary role in the memory disruptive effects of marijuana.

Show MeSH
Related in: MedlinePlus