Dataset Information

Morphine induces c-fos and junB in striatum and nucleus accumbens via D1 and N-methyl-D-aspartate receptors.

ABSTRACT: Morphine induced the c-fos and junB immediate early genes in neurons of the medial and ventral striatum and nucleus accumbens. Induction of c-fos and junB mRNA and Fos protein was blocked by naloxone, the D1 dopamine (DA) receptor antagonists SCH23390 and SCH39166, and the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist MK801. SCH23390 attenuated morphine induction of AP-1 binding in striatum, suggesting that c-fos and junB contribute to AP-1 binding. SCH23390 and MK801 did not block morphine induction of c-fos and junB in septum. Since the morphine induction of c-fos and junB in striatum and nucleus accumbens (NA) was similar to that observed with cocaine and amphetamine, these data support current concepts that limbic striatum and NA are among the brain regions that mediate drug abuse. Furthermore, since DA and NMDA receptors may mediate opiate reward and opiate induction of c-fos and junB, the DA/NMDA regulation of c-fos and junB and their target genes may produce long-term changes in the striatal and NA circuits that contribute to opiate drug abuse.

SUBMITTER: Liu J

PROVIDER: S-EPMC44641 | biostudies-literature | 1994 Aug

REPOSITORIES: biostudies-literature

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Morphine induces c-fos and junB in striatum and nucleus accumbens via D1 and N-methyl-D-aspartate receptors.

Liu J J Nickolenko J J Sharp F R FR

Proceedings of the National Academy of Sciences of the United States of America 19940801 18

Morphine induced the c-fos and junB immediate early genes in neurons of the medial and ventral striatum and nucleus accumbens. Induction of c-fos and junB mRNA and Fos protein was blocked by naloxone, the D1 dopamine (DA) receptor antagonists SCH23390 and SCH39166, and the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist MK801. SCH23390 attenuated morphine induction of AP-1 binding in striatum, suggesting that c-fos and junB contribute to AP-1 binding. SCH23390 and MK801 did not block m ...[more]

PMID: 8078918

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Project description:BackgroundOpiate addiction is associated with complex cognitive impairment, which contributes to the development of compulsive drug use and relapses. Dopamine and N-methyl-D-aspartate receptors play critical roles in opiate-induced cognitive deficits. However, the roles of D1 and D3 receptors in the N-methyl-D-aspartate/glycineB receptor-regulated cognitive behaviors induced by morphine remain unknown.MethodsThe 5-choice serial reaction time task was used to investigate the cognitive profiles associated with repeated morphine administration in D1 (D1-/-)- and D3 (D3-/-)-receptor knockout mice. The expression of phosphorylated NR1, Ca2+/calmodulin-dependent protein kinase II (CaMKII), and cAMP response element-binding protein (CREB) in the brain was examined by western blotting. D1-/- and D3-/- mice were treated with the N-methyl-D-aspartate/glycineB site agonist l-aminocyclopropanecarboxylic acid and the antagonist L-701,324 to chronically disrupt N-methyl-D-aspartate receptor function and investigate their effects on morphine-induced cognitive changes.ResultsRepeated morphine administration impaired attentional function and caused impulsive and compulsive behaviors. D1-/- mice exhibited hardly any premature nosepokes. D3-/- mice showed robustly increased morphine-induced impulsive behavior. The numbers of premature responses were decreased by L-701,324 administration and increased by ACPC administration; these effects were completely abolished in D1-/- mice due to their inability to perform reward-based tasks. In contrast, the inhibitory effects of L-701,324 on impulsive behavior were significantly augmented in D3-/- mice.ConclusionsN-methyl-D-aspartate/glycineB site functions may contribute to morphine-induced cognitive deficits, especially those related to impulsive behavior. D1 and D3 receptors may have contrasting effects with respect to modulating impulsive behavior. D3 receptors have inhibitory effects on impulsive behaviors, and these effects are clearly mediated by N-methyl-D-aspartate/glycineB receptor and μ-opioid receptor interactions.

Dataset Information

Morphine induces c-fos and junB in striatum and nucleus accumbens via D1 and N-methyl-D-aspartate receptors.

Publications

Morphine induces c-fos and junB in striatum and nucleus accumbens via D1 and N-methyl-D-aspartate receptors.

Similar Datasets

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