Thesis
Glutamate transporter modulation in morphine-conditioned place preference: implications for drug-specific mechanisms in substance use disorders
Master of Science (M.S.), Drexel University
Apr 2026
DOI:
https://doi.org/10.17918/00011349
Abstract
Glutamate plays an important role as the primary excitatory neurotransmitter in the nervous system, driving synaptic plasticity, and is implicated in the development of substance use disorders. Glutamatergic signaling is mainly regulated by the activity of glutamate transporters, key proteins that clear extracellular glutamate and regulate levels of synaptic glutamate. Modulation in the activity of EAAT2, the most abundant glutamate transporter, has been demonstrated to regulate drug seeking- and drug context seeking-behaviors in models of psychostimulant use disorder. However, it has yet to be demonstrated that EAAT2 activity modulation has a role in models of opioid use disorder, which develops through overlapping but distinct glutamatergic contributions. The current study evaluated the effects of positive allosteric modulation of EAAT2, through a compound termed NA-014, on the expression of morphine conditioned place preference (CPP) in mice. CPP was evaluated with a range of conditioning doses of morphine. A low dose of morphine (10 mg/kg) was shown to be insufficient at reliably eliciting CPP, while a high dose (20 mg/kg) elicited CPP, but showed to be resistant to extinction training. An intermediate dose (15 mg/kg) was determined to reliably elicit CPP and allowed for greater extinction of this preference compared to the high dose (20 mg/kg). Extinction training was performed via a saline-paired protocol, and reinstatement was performed using a priming dose of morphine (7.5 mg/kg). Treatment with NA-014 (60 mg/kg), a dose previously shown to reduce psychostimulant CPP without effecting locomotion, had no significant effect on CPP scores either immediately following conditioning or during reinstatement. These results suggest that positive allosteric modulation of EAAT2 activity does not alter morphine context seeking-behavior under the conditions tested. In summation, these results highlight the distinct alterations in synaptic mechanism underlying psychostimulant and opioid-related motivated behaviors and suggest that the role of glutamate in driving these behaviors may be drug-specific.
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Details
- Title
- Glutamate transporter modulation in morphine-conditioned place preference
- Creators
- Arthur Kendall Faunce Burns
- Contributors
- Andreia Mortensen (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University
- Number of pages
- 65 pages
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- College of Medicine; Neurology; Drexel University
- Other Identifier
- 991022180106504721