Nicotinic modulation of hippocampal cell signaling and associated effects on learning and memory

Kutlu, Munir Gunes; Gould, Thomas J.

doi:10.1016/j.physbeh.2015.12.008

Cited by 54 publications

(34 citation statements)

References 211 publications

(258 reference statements)

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“…In further support of nicotine modulating synaptic plasticity, nicotine can alter key cell signaling kinases and transcription factors known to modulate hippocampal learning and plasticity such as PKA, ERK1/2, and CREB (for review, see Kutlu and Gould 2016). For example, Gould et al (2014b) showed that infusions of a subthreshold dose of the PKA inhibitor PKI 14 -22 amide into the dorsal hippocampus reversed enhancement of contextual fear conditioning by acute nicotine.…”

Section: Modulation Of Hippocampal Plasticity By Nicotinementioning

confidence: 99%

“…Moreover, CREB phosphorylation in the hippocampus was also inhibited following chronic ethanol exposure while ethanol withdrawal enhanced hippocampal CREB (Bison and Crews 2003). The ethanol-induced changes in MAPK-CREB pathway are crucial to understanding the molecular mechanisms underlying the hippocampal deficits during chronic ethanol exposure because numerous studies have shown that activation of this cell signaling pathway is necessary for long-term memory formation (e.g., Atkins et al 1998;Vianna et al 2000) and LTP (e.g., Winder et al 1999;Kelleher et al 2004; for review, see Kutlu and Gould 2016). Overall, these studies show that chronic ethanol can inhibit cell signaling cascades involved in learning through activation of GABAergic receptors and blockage of NMDA receptors in the hippocampus.…”

Section: Effects Of Prolonged Alcohol Exposure On Hippocampal Functionmentioning

confidence: 99%

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Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction

2016

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It has long been hypothesized that conditioning mechanisms play major roles in addiction. Specifically, the associations between rewarding properties of drugs of abuse and the drug context can contribute to future use and facilitate the transition from initial drug use into drug dependency. On the other hand, the self-medication hypothesis of drug abuse suggests that negative consequences of drug withdrawal result in relapse to drug use as an attempt to alleviate the negative symptoms. In this review, we explored these hypotheses and the involvement of the hippocampus in the development and maintenance of addiction to widely abused drugs such as cocaine, amphetamine, nicotine, alcohol, opiates, and cannabis. Studies suggest that initial exposure to stimulants (i.e., cocaine, nicotine, and amphetamine) and alcohol may enhance hippocampal function and, therefore, the formation of augmented drug-context associations that contribute to the development of addiction. In line with the self-medication hypothesis, withdrawal from stimulants, ethanol, and cannabis results in hippocampus-dependent learning and memory deficits, which suggest that an attempt to alleviate these deficits may contribute to relapse to drug use and maintenance of addiction. Interestingly, opiate withdrawal leads to enhancement of hippocampus-dependent learning and memory. Given that a conditioned aversion to drug context develops during opiate withdrawal, the cognitive enhancement in this case may result in the formation of an augmented association between withdrawalinduced aversion and withdrawal context. Therefore, individuals with opiate addiction may return to opiate use to avoid aversive symptoms triggered by the withdrawal context. Overall, the systematic examination of the role of the hippocampus in drug addiction may help to formulate a better understanding of addiction and underlying neural substrates.Addiction is a major worldwide health problem that results in maladaptive behavioral changes, some that can last a lifetime. This behavioral plasticity, often times maladaptive, must be associated changes in neural plasticity. In fact, it has been noted multiple times that there is a high degree of overlap between the neurobiology of learning and memory and the neurobiology of addiction

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Section: Modulation Of Hippocampal Plasticity By Nicotinementioning

confidence: 99%

Section: Effects Of Prolonged Alcohol Exposure On Hippocampal Functionmentioning

confidence: 99%

Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction

2016

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“…Therefore, nicotine-induced plasticity in regions that regulate memory consolidation and learning may also mediate nicotine-seeking behavior. Nicotine has been shown to both improve working memory and to enhance hippocampal-dependent learning [230]. In contrast, chronic nicotine administration, when delivered at high doses, enhances hippocampal neurogenesis, the growth of new neurons, specifically in the dentate gyrus region of the hippocampus [231-233].…”

Section: Neurophysiological Mechanisms Underlying Nicotine-seeking Bementioning

confidence: 99%

“…In the hippocampus, nAChRs are densely expressed on inhibitory interneurons [242], and nicotine-induced hippocampal LTP is at least in part dependent on local disinhibition of granule cells [243]. Nicotine-mediated hippocampal plasticity and its role in learning and plasticity have been discussed extensively [230, 244, 245]. …”

Section: Neurophysiological Mechanisms Underlying Nicotine-seeking Bementioning

confidence: 99%

Neurobiological and Neurophysiological Mechanisms Underlying Nicotine Seeking and Smoking Relapse

2018

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Tobacco-related morbidity and mortality continue to be a significant public health concern. Unfortunately, current FDA-approved smoking cessation pharmacotherapies have limited efficacy and are associated with high rates of relapse. Therefore, a better understanding of the neurobiological and neurophysiological mechanisms that promote smoking relapse is needed to develop novel smoking cessation medications. Here, we review preclinical studies focused on identifying the neurotransmitter and neuromodulator systems that mediate nicotine relapse, often modeled in laboratory animals using the reinstatement paradigm, as well as the plasticity-dependent neurophysiological mechanisms that facilitate nicotine reinstatement. Particular emphasis is placed on how these neuroadaptations relate to smoking relapse in humans. We also highlight a number of important gaps in our understanding of the neural mechanisms underlying nicotine reinstatement and critical future directions, which may lead toward the development of novel, target pharmacotherapies for smoking cessation.

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“…Nicotinic acetylcholine receptors (nAChRs) regulate a variety of cell signaling cascades that are important for various behavioral processes such as long-term memory formation (see Kutlu & Gould, 2016 for a review). In the hippocampus, nAChRs gate calcium (Ca 2+ ) and sodium into the cell (Wonnacott, 1997).…”

Section: Introductionmentioning

confidence: 99%

Acute nicotine disrupts consolidation of contextual fear extinction and alters long-term memory-associated hippocampal kinase activity

Kutlu

Garrett

Gadiwalla

et al. 2017

Neurobiology of Learning and Memory

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Previous research has shown that acute nicotine, an agonist of nAChRs, impaired fear extinction. However, the effects of acute nicotine on consolidation of contextual fear extinction memories and associated cell signaling cascades are unknown. Therefore, we examined the effects of acute nicotine injections before (pre-extinction) and after (post-extinction) contextual fear extinction on behavior and the phosphorylation of dorsal and ventral hippocampal ERK1/2 and JNK1 and protein levels on the 1st and 3rd day of extinction. Our results showed that acute nicotine administered prior to extinction sessions downregulated the phosphorylated forms of ERK1/2 in the ventral hippocampus, but not dorsal hippocampus, and JNK1 in both dorsal and ventral hippocampus on the 3rd extinction day. These effects were absent on the 1st day of extinction. We also showed that acute nicotine administered immediately and 30 mins, but not 6 hours, following extinction impaired contextual fear extinction suggesting that acute nicotine disrupts consolidation of contextual fear extinction memories. Finally, acute nicotine injections immediately after extinction sessions upregulated the phosphorylated forms of ERK1/2 in the ventral hippocampus, but did not affect JNK1. These results show that acute nicotine impairs contextual fear extinction potentially by altering molecular processes responsible for the consolidation of extinction memories.

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Nicotinic modulation of hippocampal cell signaling and associated effects on learning and memory

Cited by 54 publications

References 211 publications

Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction

Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction

Neurobiological and Neurophysiological Mechanisms Underlying Nicotine Seeking and Smoking Relapse

Acute nicotine disrupts consolidation of contextual fear extinction and alters long-term memory-associated hippocampal kinase activity

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