Background: Hydrogen sulfide (H2S), a novel gasotransmitter, exhibits antioxidant and neuroprotective properties and has been implicated in the mitigation of neurodegenerative disorders. Objectives: The present study aims to investigate the potential protective effects of exogenous H2S, administered as sodium hydrosulfide (NaHS), on cognitive deficits in a streptozotocin (STZ)-induced rat model of Alzheimer’s disease (AD). Methods: Adult male Wistar rats (180 - 200 g) were divided into five groups: Control, Sham, STZ, STZ + Saline, and STZ + NaHS. To induce AD, STZ (3 mg/kg, 10 μL/injection site) was bilaterally administered into the lateral ventricles. Rats were then treated daily via intraperitoneal injection with saline or NaHS (5.6 mg/kg) for 21 days. Memory performance was assessed using the passive avoidance (PA) test. Results: The STZ significantly reduced step-through latency (STL) and time spent in the light compartment (TLC), while increasing time spent in the dark compartment (TDC) and the number of entries into the dark compartment. Treatment with NaHS in STZ-administered rats prevented these adverse effects. Conclusions: The results suggest that NaHS improves STZ-induced memory dysfunction in the PA test. Thus, NaHS may hold therapeutic potential for memory impairment in AD.

Objective(s): Auraptene (7-geranyloxycoumarin) (AUR), from Citrus species has shown antiinflammatory, neuroprotective, and acetylcholinesterase (AChE) and beta-secretase inhibitory effects.Scopolamine is a nonselective muscarinic receptor antagonist which causes short‐term memory impairments and is used for inducing animal model of Alzheimer’s disease (AD). This research aimed to investigate the effect of AUR on scopolamine-induced avoidance memory retention deficits in stepthrough task in mice.Materials and Methods: The effect of four‐day pre-training injections of AUR (50, 75, and 100 mg/kg, subcutaneous (SC)) and scopolamine (1 mg/kg, IP), and their co-administration on avoidance memory retention in step‐through passive avoidance task, was investigated by measuring the latency to enter to the dark chamber.Results: Pre-training administration of AUR caused significant increase in step‐through latency in comparison with control group, 48, 96, and 168 hr after training trial. The findings of this study showed that scopolamine (1 mg/kg, IP, for four consecutive days) impaired passive avoidance memory retention compared to saline-treated animals. Step-through passive avoidance task results showed that AUR markedly reversed scopolamine-induced avoidance memory retention impairments, 24 and 168 hr after training trial in step-through task.Conclusion: Results from co-administration of AUR and scopolamine showed that AUR reversed scopolamine-induced passive avoidance memory retention impairments.

Behavioural studies have suggested interactions between cholinergic and glutamatergic systems. In the present study, the effect of intra-VTA pretest administration of a nonselective muscarinic acetylcholine antagonist, scopolamine, glutamatergic drugs and their interaction on inhibitory avoidance response was investigated.Rats were anesthetized with intra-peritoneal injection of ketamine hydrochloride, plus xylazine and then placed in a stereotaxic apparatus. Also, two stainless-steel cannuale were placed in the ventral tegmental area. A step-through inhibitory avoidance task was used for memory assessment in male Wistar rats. The drug injected 5 min before testing and the step-through latency was measured with a stopwatch as inhibitory avoidance memory.The results showed that intra-VTA pretest administration of scopolamine (3 and 4 μg/rat) and NMDA receptor antagonist, MK-801 (1 and 2 μg/rat) impair memory retention. Interestingly, co-administration of an ineffective dose of MK801 (0.5 μg/rat) with ineffective doses of scopolamine (1 and 2 μg/rat) significantly decreased the inhibitory avoidance memory. Although pretest intra-VTA injections of NMDA (0.001 and 0.01 μg/rat) had no effect by itself, but its co-administration with scopolamine (4 μg/rat) prevented the decreasing effect of scopolamine on inhibitory avoidance memory retention.Our data may indicate that muscarinic and NMDA receptors in the VTA may be involved in the mechanism(s) modulating inhibitory avoidance memory retention through the VTA dopaminergic projections.

Objective: In the present study, the effects of lithium chloride (LiCl) on morphine induced state-dependent memory were examined in NMRI mice in a passive avoidance task. Method: In this experimental study one-trial step-down paradigm was used for the assessment of memory in adult male NMRI mice. Results: Administration of morphine (5 mg/kg) subcutaneously (S.C.) 30 min before training or testing induced impairment of memory formation. Injection of the same dose of the drug 30 min before testing restored retrieval of memory impaired under pre-training morphine effect. intraperitoneal (I.P.) injection of lithium, 60 min before training or prior to testing also impaired memory retrieval. Impaired memory was restored in animals that had received LiCl (80 and 160 mg/kg) as pre-test injection in cases of pre-training administration of morphine. Pre-training administration of lower doses of lithium (20 mg/kg) impaired memory storage in passive avoidance test. LiCl-induced impairment of memory was restored by pre-test administration of morphine. In animals receiving pre-training morphine, combined pre-test morphine and LiCl administration increased the restoration of memory impaired by the opioid. Conclusion: Considering the results, an interaction between state dependency of morphine and lithium might be present.

Objective: In this experiment, the effects of dopaminergic drugs on morphine state dependent memory were examined in mice, based on the passive avoidance task. Method: In this experimental research, morphine and saline were administered subcutaneously, and dopaminergic drugs were administered cerebroventricularly (into the brain). Then (using Passive Avoidance Apparatus) step-down latency was measured, which shows the memory of the animal. Results: Pre- training subcutaneous administration of morphin (5mg/kg) led to the impairment of retrieval memory but the administration of the same dose on the test day led to state-dependent memory (learning). The pre-test intracerebroventricular (ICV) administration of the D1 agonist (SKF 38393), D2 agonist (quinpirole) and D2 blocker (sulpiride) not only mimiced the effect of pre-test morphine treatment, but also increased the function of opioids. Furthermore, the pre-test ICV administration of D1 antagonist (SCH 23390) prevented the restoration of memory by morphine. Conclusion: Effects of mrphine on some memory pathways seems to be induced through dopamine receptors.