NMDA AND D-1 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 neuron s of the medial and ventral striatum following administration of morph ine. The striatal induction of c-fos and junB mRNA and Fos protein was blocked by naloxone, the D-1 dopamine (DA) receptor antagonists, SCH2 3390 and SCH39166, and the N-methyl-D-aspartate (NMDA) glutamate recep tor antagonist, MK801. SCH23390 and MK801 did not block morphine induc tion of c-fos and junB in septum. Since the pattern of the morphine in duction of c-fos and junB in striatum and nucleus accumbens was simila r to that observed with cocaine and amphetamine [2,18,45,51], these da ta 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 D-1 receptors activate the CRE (cyclase response el ement) and NMDA receptors activate the SRE (serum response element) in the c-fos promoter [1], then this data suggests that serial activatio n of mu opiate, NMDA and D-1 receptors on different neurons is require d to induce Fos in striatal neurons with D-1 receptors. Moreover, conc urrent activation of NMDA and D-1 receptors is required for Fos induct ion in striatal neurons. The Fos induced by this simultaneous activati on of NMDA and D-1 receptors should lead to long-term changes of gene expression that might also be involved in changes of brain circuits th at could form the basis for 'memories' relating to prior exposure to a ddictive drugs.