ACUTE ADMINISTRATION OF COCAINE, BUT NOT AMPHETAMINE, INCREASES THE LEVEL OF SYNAPTOTAGMIN-IV MESSENGER-RNA IN THE DORSAL STRIATUM OF RAT

Synaptotagmin IV (Syt TV) is an inducible member of a multi-gene famil y of synaptic vesicle proteins that participate in Ca2+-dependent and Ca2+-independent interactions during membrane trafficking. We have exa mined the pattern of expression of Syt IV mRNA following the administr ation 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 TV mRNA in the d orsal striatum of rats 1 h after the administration of the drug. No ch ange in the hybridization pattern of the Syt IV-specific probe to othe r regions of the rat brain were observed following cocaine or amphetam ine administration at the time points examined (1, 3, 6, 12 and 24 h). The pattern of synaptotagmin I-(Syt I) specific hybridization remaine d constant, relative to controls, for both the cocaine-and amphetamine -treated animals. Northern hybridization analysis of mRNA isolated fro m striatal tissue using oligonucleotide probes specific to Syt I and S yt IV demonstrated that the probes hybridized exclusively to transcrip ts of the sizes previously reported for these two synaptotagmins and c onfirmed that the relative level of Syt IV to Syt I mRNA increased fol lowing the administration of cocaine but not amphetamine. These result s indicate that these drugs have different effects on altering the lev els of Syt IV mRNA. This work, in conjunction with earlier work that d emonstrated that cocaine and amphetamine have different effects on the expression of immediate early genes such as c-Fos, supports the hypot hesis that these psychotropic agents evoke different patterns of gene expression which may lead to alteration in synaptic efficacy. (C) 1998 Elsevier Science B.V.