1.Involvement of dorsal hippocampus glutamatergic and nitrergic neurotransmission in autonomic responses evoked by acute restraint stress in rats.
Moraes-Neto TB1, Scopinho AA2, Biojone C1, Corrêa FM2, Resstel LB3. Neuroscience. 2014 Jan 31;258:364-73. doi: 10.1016/j.neuroscience.2013.11.022. Epub 2013 Nov 22.
The dorsal hippocampus (DH) is a structure of the limbic system that is involved in emotional, learning and memory processes. There is evidence indicating that the DH modulates cardiovascular correlates of behavioral responses to stressful stimuli. Acute restraint stress (RS) is an unavoidable stress situation that evokes marked and sustained autonomic changes, which are characterized by elevated blood pressure (BP), intense heart rate (HR) increase and a decrease in cutaneous temperature. In the present study, we investigated the involvement of an N-methyl-D-aspartate (NMDA) glutamate receptor/nitric oxide (NO) pathway of the DH in the modulation of autonomic (arterial BP, HR and tail skin temperature) responses evoked by RS in rats. Bilateral microinjection of the NMDA receptor antagonist AP-7 (10 nmol/500 nL) into the DH attenuated RS-evoked autonomic responses. Moreover, RS evoked an increase in the content of NO₂/NO₃ in the DH, which are products of the spontaneous oxidation of NO under physiological conditions that can provide an indirect measurement of NO production.
2.The dual effect of CA1 NMDA receptor modulation on ACPA-induced amnesia in step-down passive avoidance learning task.
Nasehi M1, Amin-Yavari S2, Ebrahimi-Ghiri M3, Torabi-Nami M4, Zarrindast MR5. Eur Neuropsychopharmacol. 2015 Apr;25(4):557-65. doi: 10.1016/j.euroneuro.2015.01.004. Epub 2015 Jan 16.
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.
3.Involvement of the nucleus accumbens shell glutamatergic system in ACPA-induced impairment of inhibitory avoidance memory consolidation.
Rasekhi K1, Oryan S1, Nasehi M2, Zarrindast MR3. Behav Brain Res. 2014 Aug 1;269:28-36. doi: 10.1016/j.bbr.2014.04.006. Epub 2014 Apr 13.
Interactions between cannabinoid and glutamate systems have been demonstrated in some brain areas associated with mnemonic functions. This study investigates the effects of bilateral post-training intra-nucleus accumbens (NAc) shell administrations of glutamate NMDA receptor agents on memory impairment induced by cannabinoid CB1 receptor activation during a step-through inhibitory avoidance (IA) task. Our results showed post-training administration of ACPA (CB1 receptor agonist; 3 ng/side) impairs IA memory consolidation, whereas AM251 (CB1 receptor antagonist; 0.3, 3 and 30 ng/side), NMDA (0.3, 3 and 30 ng/side), and d-AP7 (NMDA receptor antagonist; 3, 30 and 300 ng/side) were ineffective. However, co-administration of AM251 (30 ng/side) or NMDA (30 ng/side) with ACPA (3 ng/side) prevented the memory-impairing effect of ACPA. Meanwhile, co-administration of NMDA (30 ng/side) and a subthreshold dose of ACPA (0.15 ng/side) decreased memory consolidation.
4.Effects of CA1 glutamatergic systems upon memory impairments in cholestatic rats.
Hosseini N1, Nasehi M, Radahmadi M, Zarrindast MR. Behav Brain Res. 2013 Nov 1;256:636-45. doi: 10.1016/j.bbr.2013.08.018. Epub 2013 Sep 16.
BACKGROUND: Bile duct ligation (BDL) is shown to induce cholestasis-related liver function impairments as well as consequent cognitive dysfunctions (i.e. impaired learning and memory formation). Glutamatergic neurotransmission plays an important role in hippocampal modulation of learning and memory function. The present study aimed to investigate the possible involvement of dorsal hippocampal (CA1) glutamatergic systems upon cholestasis-induced amnesia.