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Intranasal Insulin: a Treatment Strategy for Addiction.

ABSTRACT: Addiction to substances such as alcohol, cocaine, opioids, and methamphetamine poses a continuing clinical and public challenge globally. Despite progress in understanding substance use disorders, challenges remain in their treatment. Some of these challenges include limited ability of therapeutics to reach the brain (blood-brain barrier), adverse systemic side effects of current medications, and importantly key aspects of addiction not addressed by currently available treatments (such as cognitive impairment). Inability to sustain abstinence or seek treatment due to cognitive deficits such as poor decision-making and impulsivity is known to cause poor treatment outcomes. In this review, we provide an evidenced-based rationale for intranasal drug delivery as a viable and safe treatment modality to bypass the blood-brain barrier and target insulin to the brain to improve the treatment of addiction. Intranasal insulin with improvement of brain cell energy and glucose metabolism, stress hormone reduction, and improved monoamine transmission may be an ideal approach for treating multiple domains of addiction including memory and impulsivity. This may provide additional benefits to enhance current treatment approaches.

SUBMITTER: Kashyap B

PROVIDER: S-EPMC7007475 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Intranasal Insulin: a Treatment Strategy for Addiction.

Kashyap Bhavani B Hanson Leah R LR Frey Ii William H WH

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20200101 1

Addiction to substances such as alcohol, cocaine, opioids, and methamphetamine poses a continuing clinical and public challenge globally. Despite progress in understanding substance use disorders, challenges remain in their treatment. Some of these challenges include limited ability of therapeutics to reach the brain (blood-brain barrier), adverse systemic side effects of current medications, and importantly key aspects of addiction not addressed by currently available treatments (such as cognit ...[more]

PMID: 31898283

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Project description:Intranasal insulin delivery is currently being used in clinical trials to test for improvement in human memory and cognition, and in particular, for lessening memory loss attributed to neurodegenerative diseases. Studies have reported the effects of short-term intranasal insulin treatment on various behaviors, but less have examined long-term effects. The olfactory bulb contains the highest density of insulin receptors in conjunction with the highest level of insulin transport within the brain. Previous research from our laboratory has demonstrated that acute insulin intranasal delivery (IND) enhanced both short- and long-term memory as well as increased two-odor discrimination in a two-choice paradigm. Herein, we investigated the behavioral and physiological effects of chronic insulin IND. Adult, male C57BL6/J mice were intranasally treated with 5?g/?l of insulin twice daily for 30 and 60days. Metabolic assessment indicated no change in body weight, caloric intake, or energy expenditure following chronic insulin IND, but an increase in the frequency of meal bouts selectively in the dark cycle. Unlike acute insulin IND, which has been shown to cause enhanced performance in odor habituation/dishabituation and two-odor discrimination tasks in mice, chronic insulin IND did not enhance olfactometry-based odorant discrimination or olfactory reversal learning. In an object memory recognition task, insulin IND-treated mice did not perform differently than controls, regardless of task duration. Biochemical analyses of the olfactory bulb revealed a modest 1.3 fold increase in IR kinase phosphorylation but no significant increase in Kv1.3 phosphorylation. Substrate phosphorylation of IR kinase downstream effectors (MAPK/ERK and Akt signaling) proved to be highly variable. These data indicate that chronic administration of insulin IND in mice fails to enhance olfactory ability, object memory recognition, or a majority of systems physiology metabolic factors - as reported to elicit a modulatory effect with acute administration. This leads to two alternative interpretations regarding long-term insulin IND in mice: 1) It causes an initial stage of insulin resistance to dampen the behaviors that would normally be modulated under acute insulin IND, but ability to clear a glucose challenge is still retained, or 2) There is a lack of behavioral modulation at high concentration of insulin attributed to the twice daily intervals of hyperinsulinemia caused by insulin IND administration without any insulin resistance, per se.

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Intranasal Insulin: a Treatment Strategy for Addiction.

Publications

Intranasal Insulin: a Treatment Strategy for Addiction.

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