arachidonylcyclopropylamide and Amnesia

In the present study, we investigated the possible participation of the endocannabinoid system in the basolateral amygdala and N-methyl-d-aspartate (NMDA) or GABA-A receptor neurotransmission in the ventral tegmental area in the memory consolidation impairment induced by morphine administration. To measure memory formation, step-through type passive avoidance apparatus was used with adult male Wistar rats. The results showed that intraperitoneal (i.p.) administration of morphine (3 and 6mg/kg) after the successful training phase had an amnestic effect and induced memory consolidation impairment. After training, injection of a selective cannabinoid CB1 receptor agonist, arachydonilcyclopropylamide (ACPA; 0.4-0.6ng/rat) plus systemic injection of an ineffective dose of morphine (0.5mg/kg, i.p.) into the basolateral amygdala impaired memory consolidation suggesting the facilitatory effect of ACPA on morphine response. Also, the results showed that the injection of bicuculline, a GABA-A receptor antagonist (0.3-0.5µg/rat) or NMDA (0.005-0.02µg/rat) into the ventral tegmental area reversed ACPA-induced potentiation of morphine response and improved memory consolidation. It should be considered that the injection of ACPA into the basolateral amygdala and the injection of bicuculline or NMDA into the ventral tegmental area alone could not affect memory consolidation. Taken together, it seems that there is a functional interaction between the basolateral amygdala endocannabinoid system and the ventral tegmental area GABAergic- or glutamatergic neurotransmission in the modulation of morphine-induced memory consolidation impairment.

Topics: Amnesia; Analgesics, Opioid; Animals; Arachidonic Acids; Avoidance Learning; Basolateral Nuclear Complex; Bicuculline; Excitatory Amino Acid Agonists; GABA-A Receptor Antagonists; Male; Memory Consolidation; Morphine; N-Methylaspartate; Rats, Wistar; Receptor, Cannabinoid, CB1; Receptors, GABA-A; Receptors, N-Methyl-D-Aspartate; Ventral Tegmental Area

The ventral hippocampus (VH) has a high distribution of cannabinoid CB1 receptors which are important in modulating stress responses. Stress exposure activates the hypothalamic-pituitary-adrenal axis (HPA) which can impact hippocampal formation to change hippocampus-based memories. The purpose of the present study was to determine the possible role of the VH cannabinoid CB1 receptors in stress-induced amnesia using a step-through passive avoidance procedure in male Wistar rats. In order to induce acute stress, the animals were placed on an elevated platform for different time periods (10, 20 and 30min). Our results indicated that post-training 20 and 30min exposure to stress, but not 10min, induced amnesia. Post-training microinjection of a cannabinoid CB1 receptor agonist, arachydonilcyclopropylamide (ACPA; 2.5-7.5ng/rat) into the VH (intra-VH) induced amnesia. Interestingly, post-training intra-VH microinjection of the same doses of ACPA improved stress-induced amnesia. On the other hand, post-training intra-VH microinjection of a selective CB1 receptor antagonist, AM-251 (20-50ng/rat) with exposure to an ineffective stress (10min) potentiated the effect of stress on memory consolidation and induced amnesia. It should be noted that post-training intra-VH microinjection of the same doses of AM-251 alone had no effect on memory consolidation. Our results revealed that post-training intra-VH microinjection of AM-251, prior to ACPA microinjection, inhibited the reversal effect of ACPA on acute elevated platform stress. Taken together, it can be concluded that exposure to post-training inescapable stress impaired memory consolidation. The impairing effects of stress on memory retrieval may be mediated by the VH cannabinoid CB1 receptors.

Topics: Amnesia; Animals; Arachidonic Acids; Hippocampus; Male; Memory Consolidation; Piperidines; Pyrazoles; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Stress, Psychological

Functional interactions between cannabinoid and alpha-2 adrenergic systems in cognitive control in the medial prefrontal cortex (mPFC) seem possible. The present study evaluated the possible role of alpha-2 adrenoceptors of the prefrontal cortex on effect of arachidonylcyclopropylamide (ACPA), a cannabinoid CB1 receptor (CB1R) agonist, in adult male Wistar rats. The animals were bilaterally implanted with chronic cannulae in the mPFC, trained in a step-through task, and tested 24 h after training to measure step-through latency. Results indicate that pre-training microinjection of ACPA (0.05 and 0.5 μg/rat) and clonidine (alpha-2 adrenoceptor agonist; 1 and 2 μg/rat) reduce memory acquisition. Pre-training subthreshold dose of clonidine (0.5 µg/rat) restored memory-impairing effect of ACPA (0.05 and 0.5 µg/rat). On the other hand, pre-training administration of the alpha-2 adrenoceptor antagonist yohimbine in all doses used (0.5, 1, and 2 μg/rat) did not affect memory acquisition by itself, while a subthreshold dose of yohimbine (2 µg/rat) potentiated memory impairment induced by ACPA (0.005 µg/rat). Finally, a subthreshold dose of SKF96365 (a Ca(2+) channel blocker) blocked clonidine and yohimbine effect of memory responses induced by ACPA. In conclusion, these data indicate that mPFC alpha-2 adrenoceptors play an important role in ACPA-induced amnesia and Ca(2+) channels have a critical role this phenomenon.

Topics: Amnesia; Animals; Arachidonic Acids; Calcium Channels; Clonidine; Dose-Response Relationship, Drug; Imidazoles; Male; Memory; Memory Disorders; Prefrontal Cortex; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Receptors, Adrenergic, alpha-2; Yohimbine

It is well documented that cannabinoids play an important role in certain hippocampal memory processes in rodents. On the other hand, N-Methyl-d-aspartate receptors (NMDARs) mediate the synaptic plasticity related to learning and memory processes which take place in the hippocampus. Such insights prompted us to investigate the influence of dorsal hippocampal (CA1) NMDA receptor agents on amnesia induced by cannabinoid CB1 receptor agonist, arachidonylcyclopropylamide (ACPA) in male mice. One-trial step-down passive avoidance and hole-board apparatuses were used to examine the memory retrieval and exploratory behaviors, respectively. Based on our findings, pre-training intraperitoneal (i.p.) administration of ACPA (0.01mg/kg) decreased memory acquisition. Moreover, pre-training intra-CA1 infusion of NMDA (0.001, 0.0125, 0.025 and 0.2µg/mouse), d-AP7 (0.5 and 1µg/mouse) or AM251 (50ng/mouse) impaired the memory acquisition. Meanwhile, NMDA-treated animals at the doses of 0.0005, 0.05 and 0.1µg/mouse acquired memory formation. In addition, intra-CA1 microinjection of NMDA (0.0005) plus different doses of ACPA potentiated the ACPA response, while NMDA (0.1) plus the lower or the higher dose of ACPA potentiated or restored the ACPA response, respectively. Further investigation revealed that a subthreshold dose of d-AP7 could potentiate the memory acquisition impairment induced by ACPA. Moreover, the subthreshold dose of AM251 did not alter the ACPA response, while the effective dose of the drug restored the memory acquisition impairment induced by ACPA. According to these results, we concluded that activation of the NMDA receptors in the CA1 mediates a dual effect on ACPA-induced amnesia in step-down passive avoidance learning task.

Topics: 2-Amino-5-phosphonovalerate; Amnesia; Analysis of Variance; Animals; Arachidonic Acids; Avoidance Learning; CA1 Region, Hippocampal; Cannabinoid Receptor Agonists; Disease Models, Animal; Dose-Response Relationship, Drug; Electroshock; Excitatory Amino Acid Antagonists; Exploratory Behavior; Male; Mice; Microinjections; N-Methylaspartate; Piperidines; Pyrazoles; Receptors, N-Methyl-D-Aspartate

Interactions between the cannabinoid and serotonin systems have been reported in many studies. In the present study, we investigated the influence of the serotonergic receptor agents on amnesia induced by the cannabinoid CB1 receptor agonist, arachydonilcyclopropylamide (ACPA). Bilateral guide-cannulae were implanted to allow intra-CA3 microinjection of the drugs. The results showed that the intra-peritoneal (i.p.) injection of ACPA induce amnesia but did not alter head dip latency, head dip counts, and locomotion. Moreover, intra-CA3 injection of M-Chlorophenylbiguanide (M-CHL, a 5-HT3 serotonin receptor agonist), Y-25130 (a 5-HT3 serotonin receptor antagonist), RS67333 (a 5-HT4 serotonin receptor agonist), and RS23597-190 (a 5-HT4 serotonin receptor antagonist) impaired memory but have no effect on head dip latency and locomotor activity. In addition, intra-CA3 injection of Y-25130, RS67333, and RS23597-190 heighten the ACPA-induced amnesia and head dip counts while did not alter head dip latency and locomotor activity. On the other hand, intra-CA3 microinjection of M-CHL could not modify the ACPA-induced amnesia, head dip latency and locomotor activity whereas increased head dip counts. It can be concluded that the amnesia induced by i.p. administration of ACPA is at least partly mediated through the serotonergic receptor mechanism in the CA3 area.

Topics: Amnesia; Aniline Compounds; Animals; Arachidonic Acids; Biguanides; Bridged Bicyclo Compounds, Heterocyclic; CA3 Region, Hippocampal; Cannabinoid Receptor Agonists; Catheters, Indwelling; Male; Mice; Oxazines; para-Aminobenzoates; Piperidines; Receptor, Cannabinoid, CB1; Receptors, Serotonin, 5-HT3; Receptors, Serotonin, 5-HT4; Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists

The present study evaluated the involvement of the dorsal hippocampal cannabinoid CB1 receptors in the combined effect of ethanol and nicotine on passive avoidance learning in adult male mice. The results indicated that pre-training administration of ethanol (1 g/kg, i.p.) impaired memory retrieval. Pre-test administration of ethanol (0.5 and 1 g/kg, i.p.) or nicotine (0.5 and 0.7 mg/kg, s.c.) significantly reversed ethanol-induced amnesia, suggesting a functional interaction between ethanol and nicotine. Pre-test microinjection of a selective CB1 receptor agonist, ACPA (3 and 5 ng/mouse), plus an ineffective dose of ethanol (0.25 g/kg) or nicotine (0.3 mg/kg) improved memory retrieval, while ACPA by itself could not reverse ethanol-induced amnesia. Pre-test intra-CA1 microinjection of a selective CB1 receptor antagonist, AM251 (0.5-2 ng/mouse), did not lead to a significant change in ethanol-induced amnesia. However, pre-test intra-CA1 microinjection of AM251 prevented the ethanol (1 g/kg) or nicotine (0.7 mg/kg) response on ethanol-induced amnesia. In order to support the involvement of the dorsal hippocampal CB1 receptors in nicotine response, the scheduled mixed treatments of AM251 (0.1-1 ng/mouse), ACPA (5 ng/mouse) and nicotine (0.3 mg/kg) were used. The results indicated that AM251 reversed the response of ACPA to the interactive effects of nicotine and ethanol in passive avoidance learning. Furthermore, pre-test intra-CA1 microinjection of the same doses of ACPA or AM251 had no effect on memory retrieval. These findings show that the cannabinoid CB1 receptors of dorsal hippocampus are important in the combined effect of ethanol and nicotine on passive avoidance learning.

Topics: Amnesia; Analysis of Variance; Animals; Arachidonic Acids; Avoidance Learning; CA1 Region, Hippocampal; Drug Interactions; Ethanol; Male; Mental Recall; Mice; Microinjections; Nicotine; Piperidines; Pyrazoles; Random Allocation; Receptor, Cannabinoid, CB1

In the present study, we investigated the influence of bilateral intra-central amygdala (intra-CeA) microinjections of N-methyl-D-aspartate (NMDA) receptor agents on amnesia induced by a cannabinoid CB1 receptor agonist, arachydonilcyclopropylamide (ACPA). This study used a step-through inhibitory (passive) avoidance task to assess memory in adult male Wistar rats. The results showed that intra-CeA administration of ACPA (2 ng/rat) immediately after training decreased inhibitory avoidance (IA) memory consolidation as evidenced by a decrease in step-through latency on the test day, which was suggestive of drug-induced amnesia. Post-training intra-CeA microinjections of NMDA (0.0001, 0.001 and 0.01 μg/rat) did not affect IA memory consolidation. However co-administration of NMDA with ACPA (2 ng/rat) prevented the impairment of IA memory consolidation that was induced by ACPA. Although post-training intra-CeA administration of the NMDA receptor antagonist, D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5; 0.01, 0.05 and 0.1 μg/rat) alone had no effect, its co-administration with an ineffective dose of ACPA (1 ng/rat) impaired IA memory consolidation. Post-training intra-CeA microinjection of an ineffective dose of D-AP5 (0.01 μg/rat) prevented an NMDA response to the impaired effect of ACPA. These results suggest that amnesia induced by intra-CeA administration of ACPA is at least partly mediated through an NMDA receptor mechanism in the Ce-A.

Topics: 2-Amino-5-phosphonovalerate; Amnesia; Amygdala; Animals; Arachidonic Acids; Avoidance Learning; Male; Microinjections; N-Methylaspartate; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Receptors, N-Methyl-D-Aspartate