DIFFERENTIAL DISTRIBUTION OF SYNAPSIN IIA AND IIB MESSENGER-RNAS IN VARIOUS BRAIN STRUCTURES AND THE EFFECT OF CHRONIC MORPHINE ADMINISTRATION ON THE REGIONAL EXPRESSION OF THESE ISOFORMS

Quantitative reverse transcriptase-polymerase chain reaction and in si tu hybridization techniques were used to determine the regional distri bution of synapsin IIa and IIb mRNAs in rat central nervous system and to assess the effect of chronic morphine administration on the gene e xpression of these two isoforms of synapsin II. These isoforms are mem bers of a family of neuron-specific phosphoproteins thought to be invo lved in the regulation of neurotransmitter release. Our data demonstra te the widespread distribution, yet regionally variable expression, of synapsin IIa and IIb mRNAs throughout the adult rat brain and spinal cord. The ratios of the relative abundance of synapsins IIa and IIb di ffered by up to 4.5-fold among the various regions studied. Synapsin I Ia and IIb mRNAs were shown to be highly concentrated in the thalamus and in the hippocampus, whereas lower concentrations were found in mos t other central nervous system structures. In this study, we show diff erential regulation by morphine of synapsins IIa and IIb in various re gions of the brain. In the striatum, a 2.4-fold increase was observed in the levels of synapsin IIa mRNA following chronic morphine regime, whereas no change was found for synapsin IIb. On the other hand, mRNA levels of synapsin IIb in spinal cord of chronically treated rats were markedly decreased (by 62%), while no alterations were observed in sy napsin IIa. Selective regulation by morphine has also been demonstrate d in several other central nervous system structures. The opiate-induc ed regulation of the gene expression of synapsin II isoforms could be viewed as one of the cellular adaptations to the persistent opiate eff ects and may be involved in the molecular mechanism underlying opiate tolerance and/or dependence.