Further proof on the role of accumbal nNOS in cocaine-seeking behavior in rats
© 2024. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences..
BACKGROUND: Cocaine use disorder (CUD) remains a severe health problem with no effective pharmacological therapy. One of the potential pharmacological strategies for CUD pharmacotherapy includes manipulations of the brain glutamatergic (Glu) system which is particularly involved in drug withdrawal and relapse. Previous research indicated a pivotal role of ionotropic N-methyl-D-aspartate (NMDA) receptors or metabotropic receptors' type 5 (mGlu5) receptors in controlling the reinstatement of cocaine. Stimulation of the above molecules results in the activation of the downstream signaling targets such as neuronal nitric oxide synthase (nNOS) and the release of nitric oxide.
METHODS: In this paper, we investigated the molecular changes in nNOS in the prefrontal cortex and nucleus accumbens following 3 and 10 days of cocaine abstinence as well as the effectiveness of nNOS blockade with the selective enzyme inhibitor N-ω-propyl-L-arginine hydrochloride (L-NPA) on cocaine seeking in male rats. The effect of L-NPA on locomotor activity in drug-naïve animals was investigated.
RESULTS: Ten-day (but not 3-day) cocaine abstinence from cocaine self-administration increased nNOS gene and protein expression in the nucleus accumbens, but not in the prefrontal cortex. L-NPA (0.5-5 mg/kg) administered peripherally did not change locomotor activity but attenuated the reinstatement induced with cocaine priming or the drug-associated conditioned cue.
CONCLUSIONS: Our findings support accumbal nNOS as an important molecular player for cocaine seeking while its inhibitors could be considered as anti-cocaine pharmacological tools in male rats.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:76 |
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| Enthalten in: |
Pharmacological reports : PR - 76(2024), 2 vom: 01. Apr., Seite 338-347 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Frankowska, Małgorzata [VerfasserIn] |
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| Links: |
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| Themen: |
Cocaine |
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| Anmerkungen: |
Date Completed 16.04.2024 Date Revised 16.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s43440-024-00571-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369703634 |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences. | ||
| 520 | |a BACKGROUND: Cocaine use disorder (CUD) remains a severe health problem with no effective pharmacological therapy. One of the potential pharmacological strategies for CUD pharmacotherapy includes manipulations of the brain glutamatergic (Glu) system which is particularly involved in drug withdrawal and relapse. Previous research indicated a pivotal role of ionotropic N-methyl-D-aspartate (NMDA) receptors or metabotropic receptors' type 5 (mGlu5) receptors in controlling the reinstatement of cocaine. Stimulation of the above molecules results in the activation of the downstream signaling targets such as neuronal nitric oxide synthase (nNOS) and the release of nitric oxide | ||
| 520 | |a METHODS: In this paper, we investigated the molecular changes in nNOS in the prefrontal cortex and nucleus accumbens following 3 and 10 days of cocaine abstinence as well as the effectiveness of nNOS blockade with the selective enzyme inhibitor N-ω-propyl-L-arginine hydrochloride (L-NPA) on cocaine seeking in male rats. The effect of L-NPA on locomotor activity in drug-naïve animals was investigated | ||
| 520 | |a RESULTS: Ten-day (but not 3-day) cocaine abstinence from cocaine self-administration increased nNOS gene and protein expression in the nucleus accumbens, but not in the prefrontal cortex. L-NPA (0.5-5 mg/kg) administered peripherally did not change locomotor activity but attenuated the reinstatement induced with cocaine priming or the drug-associated conditioned cue | ||
| 520 | |a CONCLUSIONS: Our findings support accumbal nNOS as an important molecular player for cocaine seeking while its inhibitors could be considered as anti-cocaine pharmacological tools in male rats | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cocaine | |
| 650 | 4 | |a Drug seeking | |
| 650 | 4 | |a Nitric oxide synthase | |
| 650 | 4 | |a Nucleus accumbens | |
| 650 | 4 | |a Rats | |
| 650 | 7 | |a Nitric Oxide Synthase Type I |2 NLM | |
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| 700 | 1 | |a Gawlińska, Kinga |e verfasserin |4 aut | |
| 700 | 1 | |a Pieniążek, Renata |e verfasserin |4 aut | |
| 700 | 1 | |a Filip, Małgorzata |e verfasserin |4 aut | |
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