NMDA and D₁ receptors mediate induction of c-fos and junB genes in striatum following morphine administration: implications for studies of memory

The c-fos and junB immediate early genes (IEGs) were induced in neurons of the medial and ventral striatum following administration of morphine. The striatal 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 and MK801 did not block morphine induction of c-fos and junB in septum. Since the pattern of the morphine induction of c-fos and junB in striatum and nucleus accumbens was similar to that observed with cocaine and amphetamine [2,18,45,51], these data support current concepts that limbic striatum and nucleus accumbens are among the brain regions that mediate drug abuse [9,10,23,27,49]. If it is true that D₁ receptors activate the CRE (cyclase response element) and NMDA receptors activate the SRE (serum response element) in the c-fos promoter [1], then this data suggests that serial activation of μ opiate, NMDA and D₁ receptors on different neurons is required to induced Fos in striatal neurons with D₁ receptors. Moreover, concurrent activation of NMDA and D₁ receptors is required for Fos induction in striatal neurons. The Fos induced by this simultaneous activation of NMDA and D₁ receptors should lead to long-term changes of gene expression that might also be involved in changes of brain circuits that could form the basis for 'memories' relating to prior exposure to addictive drugs.