Acute administration of cocaine, but not amphetamine, increases the level of synaptotagmin IV mRNA in the dorsal striatum of rat

Abstract Synaptotagmin IV (Syt IV) is an inducible member of a multi-gene family of synaptic vesicle proteins that participate in Ca 2+ -dependent and Ca 2+ -independent interactions during membrane trafficking. We have examined the pattern of expression of Syt IV mRNA following the administration of cocaine and amphetamine. A single acute dose of cocaine, but not amphetamine, resulted in a transient increase, as determined by in situ hybridization, in the steady-state level of Syt IV mRNA in the dorsal striatum of rats 1 h after the administration of the drug. No change in the hybridization pattern of the Syt IV-specific probe to other regions of the rat brain were observed following cocaine or amphetamine administration at the time points examined (1, 3, 6, 12 and 24 h). The pattern of synaptotagmin I-(Syt I) specific hybridization remained constant, relative to controls, for both the cocaine- and amphetamine-treated animals. Northern hybridization analysis of mRNA isolated from striatal tissue using oligonucleotide probes specific to Syt I and Syt IV demonstrated that the probes hybridized exclusively to transcripts of the sizes previously reported for these two synaptotagmins and confirmed that the relative level of Syt IV to Syt I mRNA increased following the administration of cocaine but not amphetamine. These results indicate that these drugs have different effects on altering the levels of Syt IV mRNA. This work, in conjunction with earlier work that demonstrated that cocaine and amphetamine have different effects on the expression of immediate early genes such as c-Fos, supports the hypothesis that these psychotropic agents evoke different patterns of gene expression which may lead to alteration in synaptic efficacy.