Research ArticleActivation and Inactivation of Nicotinic Receptnors in the Dorsal Hippocampal Region Restored Negative Effects of Total (TSD) and REM Sleep Deprivation (RSD) on Memory Acquisition, Locomotor Activity and Pain Perception
Introduction
In today’s world, prolonged wakefulness is a widespread phenomenon, which is related to acute Sleep deprivation (SD) or chronic partial sleep limitation (Alhola and Polo-Kantola, 2007). Birds and mammals have two types of sleep including non-rapid eye movements (Non-REM) and rapid eye movements (REM), which are easily distinguished by electroencephalogram (EEG) and electromyogram (EMG) analysis (Lesku et al., 2008). Sleep is crucial for proper cognitive functions (Abel et al., 2013). It has been reported that lack of sleep or sleep disorders can impair attention, decision-making, learning, and various types of memory (Abel et al., 2013).
Hippocampus, is one of the brain regions that modulates cognitive functions (Lavenex et al., 2007). The hippocampal formation receives multi-modal sensory information from different cortical sources and has a significant role in learning and memory processes, spatial coding and regulating emotional behaviors (Kreutzmann et al., 2015). Furthermore, the hippocampus has a relationship with acute and chronic pain (Wang et al., 2016). Numerous studies including anatomical and behavioral experiments, and electrophysiology and molecular researches have revealed that, hippocampal formation is involved in pain information processing (Liu and Chen, 2009). Interestingly, the role of hippocampal nicotinic acetylcholine receptors in modulating pain has been reported (Chen et al., 2016). In addition, CA1 muscarinic acetylcholine receptors affect pain perception in sleep-deprived rats (Javad-Moosavi et al., 2017).
Numerous studies have indicated that pre-train SD impairs learning and memory in various types of cognitive tasks (Abel et al., 2013). In addition, it seems that hippocampus-dependent memory consolidation is sensitive to sleep disorder during the sleep phase immediately after learning (Kreutzmann et al., 2015). Indeed, sleep is significantly involved in memory consolidation and the hippocampus is a vulnerable brain region under SD conditions (Kreutzmann et al., 2015). Evidence suggests that SD disrupts the neuronal and memory formation processing in the hippocampus via reduction in Long-Term Potentiation (LTP) (Ishikawa et al., 2006), cAMP/PKA signaling (Vecsey et al., 2009), expression of glutamate receptors (Ravassard et al., 2009) and transcription of cAMP response element binding (CREB) intermediary gene (Alhaider et al., 2011).
Different stages of sleep and wakefulness are affected by specific types of neurotransmitters and receptors such as acetylcholine, serotonin and glutamate (Brown et al., 2012, Watson et al., 2012). Acetylcholine (Ach) is secreted by all neurons in the CNS and found in the basal forebrain. Basal forebrain is a structure that sends its branches into the hippocampus, neo-cortex and poly-midbrain cholinergic complex (Brown et al., 2012). Ach is involved in modulating sleep, wakefulness, learning and memory processes (Irmak and de Lecea, 2014). Ach receptors are composed of two main groups of muscarinic (mAchRs) and nicotinic cholinergic receptors (nAchRs), based on pharmacologic features. Both groups are found abundantly in the brain. nAchRs are the members of a superfamily of ligand gate ionic channels (Pohanka, 2012) and mostly located presynaptic on glutamatergic axon terminals that facilitate glutamate releasing (Hefco et al., 2003). It has been revealed that the posterior hippocampus (CA1 region, involved in learning and memory) has massive numbers of nAchRs (Parfitt et al., 2012). According to previous studies, Ach is increased during consciousness and REM sleep, and is decreased during Non-REM sleep (Irmak and de Lecea, 2014).
Sleep affects pain information processing (Bjurstrom and Irwin, 2019). It seems that similar neurobiological systems modulate pain information processing and sleep/wakefulness cycle (Foo and Mason, 2003). Furthermore, a poor sleep can alter pain information processing (Lautenbacher et al., 2006). Note that, the effects of sleep disorders, TSD (total SD) and RSD (REM SD) on pain perception are inconsistent (Lautenbacher et al., 2006). Interestingly, nAchRs are involved in pain information processing (Xanthos et al., 2015). Previous study has shown that nAchRs play a significant role in mediating stress-induced analgesia in mice (Ghasemzadeh and Rezayof, 2015).
According to the mentioned points, the main goal of the present study is to investigate the role of CA1 nAchRs in TSD/RSD-induced behavioral changes.
Section snippets
Animals
140 male Wistar rats (220–250 g, 9–10 weeks old) were used in this research. All rats were obtained from Institute for Cognitive Science Studies (ICSS), Tehran, Iran. Plexiglas cages were used to keep rats under standard temperature (22 ± 2 °C) and light/dark cycle (12/12 h). All rats had free access to food and water, except during the tests. Each experimental group consisted of seven male rats and each rat was used once. All behavioral experiments were done during the light phase. Our
Experiment 1: effects of pre-train intra-CA1 injection of nicotine or mecamylamine on memory acquisition, pain perception and locomotor activities
Eight groups of rats (56 rats) were allocated to this experiment. The rats received saline (1 µL/rat), different doses of nicotine (0.0001, 0.001, 0.01 and 0.1 µg/rat) or mecamylamine (0.001, 0.01 and 0.1 µg/rat). All injections were pre-train. This experiment was done to specify subthreshold and effective doses of each drug in normal condition.
Experiment 2: effects of TSD on memory acquisition, pain perception and locomotor activities in presence and absence of nicotine or mecamylamine
Six groups of rats (42 rats) were allocated to this experiment. The rats received intra-CA1 injection of saline (1 µL/rat), nicotine (0.0001 µg/rat) or
Effects of pre-train intra-CA1 injection of nicotine and mecamylamine on memory acquisition, pain perception and locomotor activities
The results of Shapiro-Wilk analysis showed that, the data of all experimental groups for memory acquisition: [Saline: P = 0.454, Nicotine: (0.0001 µg/rat: P = 0.052), (0.001 µg/rat: P = 0.343), (0.01 µg/rat: P = 0.516), (0.1 µg/rat: P = 0.131) and Mecamylamine: (0.001 µg/rat: P = 0.133), (0.01 µg/rat: P = 0.165), (0.1 µg/rat: 0.054)], pain perception: [Saline: P = 0.930, Nicotine: (0.0001 µg/rat: P = 0.307), (0.001 µg/rat: P = 0.536), (0.01 µg/rat: P = 0.163), (0.1 µg/rat: P = 0.624) and
Nicotine and mecamylamine impaired memory acquisition and increased locomotor activity in normal rats
The present study showed that some doses of nicotine reduced the memory acquisition in normal rats, while other doses of this drug did not influence the memory formation. Furthermore, all doses of nicotine did not alter pain perception, while only the higher doses increased locomotor activities. In addition, higher doses of mecamylamine impaired the memory acquisition. Meanwhile, mecamylamine did not alter pain perception, while its higher doses enhanced the locomotor activity.
Several studies
Funding information
There is no providing financial support to this project.
Conflict of interest
The authors declare that they have no conflict of interest.
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