Acute and chronic glutamate NMDA antagonist treatment attenuates dopamine D 1 antagonist-induced reduction of nicotine self-administration in female rats

Multiple interacting neural systems are involved in sustaining nicotine reinforcement. We and others have shown that dopamine D receptors and glutamate NMDA receptors both play important roles in nicotine reinforcement. Blockade of D receptors with the antagonist SCH-23390 (0.02 mg/kg) both acutely...

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Published inPharmacology, biochemistry and behavior Vol. 234; p. 173678
Main Authors Natarajan, Sarabesh, Abass, Grant, Kim, Lucas, Wells, Corinne, Rezvani, Amir H, Levin, Edward D
Format Journal Article
LanguageEnglish
Published United States 01.01.2024
Subjects
Animals
Benzazepines - pharmacology
Dopamine
Dopamine Antagonists - pharmacology
Excitatory Amino Acid Antagonists - pharmacology
Female
Memantine - pharmacology
N-Methylaspartate
Nicotine - pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Dopamine D1 - metabolism
Receptors, N-Methyl-D-Aspartate
Self-administration
Memantine
D
SCH-23390
NMDA
Rats
Antagonists
Nicotine
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Summary:Multiple interacting neural systems are involved in sustaining nicotine reinforcement. We and others have shown that dopamine D receptors and glutamate NMDA receptors both play important roles in nicotine reinforcement. Blockade of D receptors with the antagonist SCH-23390 (0.02 mg/kg) both acutely and chronically significantly decreased nicotine self-administration in rats. Blockade of NMDA receptors (10 mg/kg) acutely with memantine significantly increased nicotine self-administration, but chronic blockade of NMDA receptors with memantine significantly decreased nicotine self-administration. The current study examined the interactions of acute and chronic administration of SCH-23390 and memantine on nicotine self-administration in female rats. Replicating earlier studies, acute and chronic SCH-23390 significantly decreased nicotine self-administration and memantine had a biphasic effect with acute administration increasing nicotine self-administration and chronic memantine showed a non-significant trend toward decreasing it. However, chronic interaction study showed that memantine significantly attenuated the decrease in nicotine self-administration caused by chronic SCH-23390. These studies provide important information that memantine attenuates the efficacy of D antagonist SCH 23390 in reducing nicotine-self-administration. These two drugs do not appear to have mutually potentiating effects to aid tobacco cessation.
ISSN:1873-5177