Marijuana Intoxication in Rats: Interruption of Recent Memory and Effect on Brain Concentration of Delta 9-Tetrahydrocannabinol

Essman, Eric J.

doi:10.2466/pr0.1984.55.2.563

Cited by 9 publications

(10 citation statements)

References 9 publications

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“…The results of the present study add to a growing body of evidence that THC acutely impairs memory (Essman, 1984;Heyser et al, 1993;Lichtman and Martin, 1996;Mallet and Beninger, 1998;Varvel et al, 2001). In addition, results revealed that MDMA alone did not significantly affect memory at the low or medium doses tested, but MDMA at these doses interacted with THC to produce an impairment of memory that was greater than that observed with THC alone.…”

Section: Discussionsupporting

confidence: 77%

Co-administration of THC and MDMA (‘Ecstasy’) Synergistically Disrupts Memory in Rats

Young

McGregor

Mallet

2005

Neuropsychopharmacol

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3,4-Methylenedioxymethamphetamine (MDMA, 'Ecstasy') and cannabis are two of the most commonly used illicit drugs in the western world, and are often used in combination. Very little research has examined their effect on cognitive function or behavior when combined. The present study used a double Y-maze task to examine the acute effect of MDMA and D 9 -tetrahydrocannabinol (THC, the principal psychoactive ingredient of cannabis) on mnemonic function in rats, at a range of doses representative of common human use. Experiment 1 (low doses) examined the effect of 0.25 mg/kg THC and 1.25 mg/kg MDMA alone and together. At these doses MDMA or THC given alone had no effect on working memory, but the co-administered drugs significantly disrupted working memory. Experiment 2 (medium doses) examined the effect of 0.5 mg/kg THC and 2.5 mg/kg MDMA given alone or together. At these doses THC, but not MDMA, impaired working memory. Although MDMA alone had no effect, it exacerbated the impairment due to THC when the drugs were co-administered. Experiment 3 (high doses) examined the effects of 1 mg/kg THC and 5 mg/kg MDMA alone and together. Both drugs significantly impaired memory when given alone, although the impairment due to MDMA was less than that caused by THC. When co-administered at these doses, the drugs caused a major disruption of behavior and this precluded ascribing a mnemonic cause to poor performance on the double Y-maze task. Taken together, these experiments demonstrate a synergistic disruption of working memory by acute co-administration of THC and MDMA.

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Section: Discussionsupporting

confidence: 77%

Co-administration of THC and MDMA (‘Ecstasy’) Synergistically Disrupts Memory in Rats

Young

McGregor

Mallet

2005

Neuropsychopharmacol

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“…Although the adverse affects of marijuana on memory and cognitive function have long been ascribed to its actions in the hippocampus (Drew and Miller, 1974;Miller and Branconnier, 1983;Essman, 1984;Hampson and Deadwyler, 1998), the descrip-tion of CB binding sites in this brain region has provided strong corroborative evidence in favor of this hypothesis Howlett et al, 1990;Breivogel and Childers, 1998). Furthermore, the development of potent ligands for the CB1 receptor has provided a means to directly assess the effects of CBs in the CNS (Pertwee, 1997).…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Cannabinoid Inhibition of GABA_ASynaptic Transmission in the Hippocampus

2000

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The localization of cannabinoid (CB) receptors to GABAergic interneurons in the hippocampus indicates that CBs may modulate GABAergic function and thereby mediate some of the disruptive effects of marijuana on spatial memory and sensory processing. To investigate the possible mechanisms through which CB receptors may modulate GABAergic neurotransmission in the hippocampus, whole-cell voltage-clamp recordings were performed on CA1 pyramidal neurons in rat brain slices. Stimulus-evoked GABA(A) receptor-mediated IPSCs were reduced in a concentration-dependent manner by the CB receptor agonist WIN 55,212-2 (EC(50) of 138 nM). This effect was blocked by the CB1 receptor antagonist SR141716A (1 microM) but not by the opioid antagonist naloxone. In contrast, evoked GABA(B)-mediated IPSCs were insensitive to the CB agonist. WIN 55,212-2 also reduced the frequency of spontaneous, action potential-dependent IPSCs (sIPSCs), without altering action potential-independent miniature IPSCs (mIPSCs), measured while sodium channels were blocked by tetrodotoxin (TTX). Blockade of voltage-dependent calcium channels (VDCCs) by cadmium also eliminated the effect of WIN 55,212-2 on sIPSCs. Depolarization of inhibitory terminals with elevated extracellular potassium caused a large increase in the frequency of mIPSCs that was inhibited by both cadmium and WIN 55,212-2. The presynaptic effect of WIN 55,212-2 was also investigated using the potassium channel blockers barium and 4-aminopyridine. Neither of these agents significantly altered the effect of WIN 55,212-2 on evoked IPSCs. Together, these data suggest that presynaptic CB1 receptors reduce GABA(A)- but not GABA(B)-mediated synaptic inhibition of CA1 pyramidal neurons by inhibiting VDCCs located on inhibitory nerve terminals.

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“…It is well established that marijuana or its principle psychoactive ingredient, ∆ 9 -tetrahydrocannabinol (THC), impairs memory in animals (Essman 1984;Nakamura et al 1991;Heyser et al 1993) and in humans (for review, see Miller and Branconnier 1983). Similarly, the synthetic cannabinoids CP-55,940 or WIN-55,212-2 impair memory in rats (Lichtman et al 1995).…”

Section: Introductionmentioning

confidence: 96%

The cannabinoid CB 1 receptor antagonist SR141716A attenuates the memory impairment produced by ? 9 -tetrahydrocannabinol or anandamide

Mallet¹,

Beninger²

1998

Psychopharmacology

170

107

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The administration of delta9-tetrahydrocannabinol (THC), the principle psychoactive ingredient in marijuana, or the endogenous cannabinoid anandamide, has been shown to impair recent memory. The purpose of the present investigation was to determine if the cannabinoid CB1 receptor antagonist SR141716A could attenuate THC- or anandamide-induced memory impairment, and to assess the effects on memory of SR141716A alone. Memory was assessed in rats well-trained in a two-component instrumental discrimination task, consisting of a conditional discrimination, and a non-match-to-position to assess recent or working memory. SR141716A (0.0-2.0 mg/kg) had no effect on either the conditional discrimination or the non-match-to-position. However, SR141716A (0.0-2.0 mg/kg) attenuated the memory impairment produced by THC (2.0 or 4.0 mg/kg) as indexed by an enhancement of performance in the non-match-to-position. When administered to rats pretreated with anandamide (2.0 mg/kg), SR141716A (0.0-2.5 mg/kg) impaired performance in the conditional discrimination at the highest dose. This was interpreted as a deficit in some capacity unrelated to memory (e.g., motor impairment). However, lower doses of SR141716A (0.1 and 0.5 mg/kg) attenuated the anandamide-induced impairment of performance in the non-match-to-position without affecting the conditional discrimination. This is the first report that the memory impairment produced by anandamide can be attenuated by a cannabinoid antagonist; results suggest that anandamide-induced memory disruption is mediated by CB receptors.

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Marijuana Intoxication in Rats: Interruption of Recent Memory and Effect on Brain Concentration of Delta 9-Tetrahydrocannabinol

Cited by 9 publications

References 9 publications

Co-administration of THC and MDMA (‘Ecstasy’) Synergistically Disrupts Memory in Rats

Co-administration of THC and MDMA (‘Ecstasy’) Synergistically Disrupts Memory in Rats

Mechanisms of Cannabinoid Inhibition of GABA_ASynaptic Transmission in the Hippocampus

The cannabinoid CB 1 receptor antagonist SR141716A attenuates the memory impairment produced by ? 9 -tetrahydrocannabinol or anandamide

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Marijuana Intoxication in Rats: Interruption of Recent Memory and Effect on Brain Concentration of Delta 9-Tetrahydrocannabinol

Cited by 9 publications

References 9 publications

Co-administration of THC and MDMA (‘Ecstasy’) Synergistically Disrupts Memory in Rats

Co-administration of THC and MDMA (‘Ecstasy’) Synergistically Disrupts Memory in Rats

Mechanisms of Cannabinoid Inhibition of GABAASynaptic Transmission in the Hippocampus

The cannabinoid CB 1 receptor antagonist SR141716A attenuates the memory impairment produced by ? 9 -tetrahydrocannabinol or anandamide

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Product

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Mechanisms of Cannabinoid Inhibition of GABA_ASynaptic Transmission in the Hippocampus