Dopaminergic D1 receptor agonist SKF 38393 induces GAP-43 expression and long-term potentiation in hippocampus in vivo.
We evaluated whether activating dopamine D1 receptors (D1R) with an agonist will mimic the effects of long-term potentiation (LTP)-inducing electrical stimulation and trigger the expression of the presynaptic growth-associated protein 43 (GAP-43), a putative synaptic plasticity factor. Thus, we conducted GAP-43 protein analyses together with assessments of LTP across CA3/CA1 synapses in guinea pigs administered with SKF38393 (the D1R agonist) and/or SCH23390 (the D1R antagonist). Our results showed that guinea pigs treated with SKF38393 coupled with low-frequency stimulation gradually exhibited an LTP-like potentiation in correlation with increased GAP-43 protein expression. However, when SKF38393 treatment was preceded by administration of SCH23390, this antagonized the occurrence of both synaptic potentiation and GAP-43 up-regulation. By comparison, persistent LTP was readily expressed after brief high frequency tetanic stimulation in control guinea pigs, whereas animals injected with SCH23390 and tetanized only developed early-LTP but not late-LTP. Western blot analyses showed GAP-43 up-regulation in the tetanized control guinea pigs but not those injected with SCH23390. We conclude that direct D1R activations with an agonist can mimic LTP-inducing electrical stimulation to produce GAP-43 up-regulation and synaptic plasticity.
Williams
Shimere
S
Division of Neurobiology and Neurotoxicology, Department of Biomedical Sciences, Meharry Medical College, 1005 D.B. Todd Blvd., Nashville, TN 37208, USA.
Mmbaga
Natu
N
Chirwa
Sanika
S