Differential Expression of Doublecortin-Like Kinase Gene Products in the Striatum of Behaviorally Hyperresponsive Rats
Behavioral hyperresponsiveness entails major changes in neuronal plasticity, such as augmented striatal dopaminergic neurotransmission and changes in neuronal morphology. These two processes may be related via mechanisms involving Ca2+/calmodulin-dependent protein kinases (CaMK). Dopaminergic regulation of a newly characterized CaMK-like gene, i.e., doublecortin-like kinase (DCLK), has been reported. However, it is not known if and how CaMK-like splice variants of the gene are responsive in behavioral hyperresponsiveness induced by enhanced dopaminergic neurotransmission. We, therefore, measured with quantitative in situ hybridization levels of mRNA encoding the CaMK domain-containing gene product, called DCLK or a CaMK domain-lacking variant called CaMK-related peptide (CARP) in the rat striatum. We have applied three forms of behavioral hyperresponsiveness, viz. administration of selective dopamine agonists to animals with a unilaterally dopamine-depleted striatum and psychomotor sensitization to amphetamine or morphine. DCLK mRNA only showed changes after dopamine depletion, but not after subsequent treatment with dopamine agonists during expression of amphetamine or morphine sensitization. In contrast, CARP mRNA was dramatically increased in the dopamine-depleted striatum after administration of a dopamine D1 agonist. Furthermore, CARP was upregulated and downregulated during expression of amphetamine and morphine sensitization, respectively.
CARP is suggested to play a role in morphological plasticity. We, therefore, propose that the observed changes are involved in dopamine-induced changes in striatal neuronal circuitry. A hypothetical model of action of CARP is presented.
KeywordsDopamine Cage Morphine Cocaine Hydrochloride
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