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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 126 (1996), S. 125-131 
    ISSN: 1432-2072
    Keywords: Radial-arm maze ; Δ9-Tetrahydrocannabinol (Δ9-THC) ; Scopolamine ; Physostigmine ; SR141716A ; Cannabinoid antagonist ; Working memory
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of the present study was to investigate whether the cannabinoid and cholinergic systems impair working memory through a common mechanism. This hypothesis was tested by examining whether the cannabinoid antagonist SR141716A would ameliorate radial-arm performance deficits caused by either the naturally occurring cannabinoid, Δ9-THC, or scopolamine, a muscarinic antagonist. In addition, we evaluated whether the cholinesterase inhibitor, physostigmine, would prevent Δ9-THC-induced impairment of spatial memory. Finally, because the locomotor suppressive effects of cannabinoids may decrease radial arm choice accuracy independent of a direct effect on memory, we examined the impact of increasing the intertrial error on radial arm choice accuracy. As previously reported, Δ9-THC impaired maze performance (ED50=3.0 mg/kg). Increasing the intertrial interval from 5 s to 30 s resulted in a three-fold increase in the amount of time required to complete the maze without affecting choice accuracy. Importantly, SR141716A prevented Δ9-THC-induced deficits in radial-arm choice accuracy in a dose-dependent manner (AD50=2.4 mg/kg); however, the cannabinoid antagonist failed to improve the disruptive effects of scopolamine. Conversely, physostigmine failed to improve performance deficits produced by Δ9-THC. These data provide strong evidence that Δ9-THC impairs working memory through direct action at cannabinoid receptors. Moreover, these results suggest that scopolamine and Δ9-THC do not impair spatial memory in a common serial pathway, though they may converge on a third neurochemical system.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 119 (1995), S. 282-290 
    ISSN: 1432-2072
    Keywords: Radial-arm maze ; Δ9-tetrahydrocannabinol (Δ9-THC) ; CP-55,940 ; WIN-55,212-2 ; Anandamide ; Cannabidiol ; Hippocampus ; Antinociception ; Catalepsy ; Rectal temperature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of the present study was to investigate the disruptive effects of cannabinoids on working memory as assessed in the eight-arm radial-maze. Systemic administration of Δ9-THC, WIN-55,212-2, and CP-55,940 increased the number of errors committed in the radial-maze. CP-55,940 was the most potent cannabinoid in impairing memory (ED50=0.13 mg/kg). Δ9-THC and WIN-55,212-2 disrupted mazechoice accuracy at equipotent doses (ED50 values =2.1 and 2.2 mg/kg, respectively). In addition, systemic administration of each of these agents retarded completion time. Whereas the doses of Δ9-THC and CP-55,940 required to retard maze performance were higher than those needed to increase error numbers, WIN-55,212-2 was equipotent in both of these measures. On the other hand, neither anandamide, the putative endogenous cannabinoid ligand, nor cannabidiol, an inactive naturally occurring cannabinoid, had any apparent effects on memory. A second aim of this study was to elucidate the neuroanatomical substrates mediating the disruptive effects of cannabinoids on memory. Intrahippocampal injections of CP-55,940 impaired maze performance in a dose-dependent manner (ED50=8 µg/rat), but did not retard the amount of time required to complete the maze. The effects of intrahippocampal CP-55,940 were apparently specific to cognition because no other cannabinoid pharmacological effects (e.g., antinociception, hypothermia, and catalepsy) were detected. This dissociation between choice accuracy in the radial-maze and other cannabinoid pharmacological effects suggests that the working memory deficits produced by cannabinoids may be mediated by cannabinoid receptors in the hippocampus.
    Type of Medium: Electronic Resource
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