The Effects of Intranasal Galanin on Morphine Induced Conditioned Place Preference Restricted; Files Only
Guo, Eugene (Spring 2026)
Abstract
Opioid Use Disorder (OUD) is driven in part by the reinforcing effects of opioids on mesolimbic dopamine circuitry. Galanin, an endogenous neuropeptide, has been shown to attenuate opioid reward when administered intracerebroventricularly (ICV), but its therapeutic application is limited by poor blood-brain barrier permeability. This study investigated whether intranasal (IN) delivery of galanin in nanoparticle form could non-invasively access the central nervous system (CNS) and modulate opioid reward-related behavior. A flurothyl-induced seizure susceptibility assay was first used to validate CNS delivery. IN galanin nanoparticles (1.4mg total; 140µg galanin, 10% loading) produced a borderline significant decrease in generalized tonic-clonic seizure onset latency, strongly suggesting successful CNS penetration. To assess opioid reward, a morphine conditioned place preference (CPP) paradigm was conducted. Morphine (1mg/kg) induced a significant place preference. However, IN galanin nanoparticles (0.5mg total; 50µg galanin, 10% loading) did not significantly attenuate CPP, regardless of whether the mice received IN vehicle or galanin, although the galanin-treated group showed a non-significant trend toward reduced reward. Despite this, the galanin-treated group showed a lower mean preference, suggesting a possible trend toward reduced reward. Analyses of locomotion on CPP conditioning days indicated that galanin did not alter morphine-induced change in activity. Midbrain galanin levels were measured using ELISA following IN administration, but results were inconclusive due to methodological issues with sample preparation. These findings suggest that IN galanin is a promising novel method for CNS galanin delivery, but does not robustly attenuate morphine reward under the conditions tested. Limitations of the study include issues with delivery efficiency, dosing assay reliability, and animal numbers, which likely contributed to these results. Future work optimizing the approaches are necessary to better evaluate the therapeutic potential of IN galanin in OUD.
Table of Contents
Introduction...1
Background on Opioid Epidemic...1
Figure 1: Three waves of the opioid epidemic...2
The Effects of Morphine and Other Opioids on Reward Circuitry...2
Figure 2: Opioid reward circuitry in the mouse brain...3
Galanin as a Modulator of the Opioid Reward Circuit...4
The Blood Brain Barrier (BBB) as an obstacle to non-invasive drug delivery...6
Figure 3: Intranasal delivery pathway through olfactory and trigeminal nerves...7
Validating IN galanin delivery to the CNS through a Seizure Susceptibility Assay...8
Studying Abuse Liability via Conditioned Place Preference...9
Aims and Hypothesis...10
Methods...11
Animals...11
Drugs...11
IN galanin nanoparticle encapsulation and administration...12
Seizure Susceptibility Assay...12
Figure 4: Flurothyl Chamber Setup...13
IN Galanin Morphine Conditioned Place Preference (CPP) Assay...13
Figure 5: CPP Chamber Setup...14
Midbrain Galanin ELISA Assay...15
Figure 6: Midbrain collection for Galanin ELISA...15
Statistical Analysis...16
Results...17
Figure 7: IN galanin shows borderline significance in decreasing flurothyl-induced GTCS onset latency...17
Figure 8: IN galanin does not significantly attenuate morphine induced CPP...19
Figure 9: Morphine administration alters locomotor activity, but is not affected by galanin treatment...20
Figure 10: Mibrain galanin concentration measured by ELISA...21
Discussion...22
Conclusion...28
Works Cited...29
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File download under embargo until 28 May 2028 | 2026-04-21 18:35:06 -0400 | File download under embargo until 28 May 2028 |
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