Korean J Physiol Pharmacol.  2008 Dec;12(6):293-297. 10.4196/kjpp.2008.12.6.293.

Forskolin Enhances Synaptic Transmission in Rat Dorsal Striatum through NMDA Receptors and PKA in Different Phases

• Cho HS
• Lee HH
• Choi SJ
• Kim KJ
• Jeun SH
• Li QZ
• Sung KW

• KMID: 2285355
• DOI: http://doi.org/10.4196/kjpp.2008.12.6.293

Abstract

The effect of forskolin on corticostriatal synaptic transmission was examined by recording excitatory postsynaptic currents (EPSCs) in rat brain slices using the whole-cell voltage-clamp technique. Forskolin produced a dose-dependent increase of corticostriatal EPSCs (1, 3, 10, and 30micrometer) immediately after its treatment, and the increase at 10 and 30micrometer was maintained even after its washout. When the brain slices were pre-treated with (DL)-2-amino-5-phosphonovaleric acid (AP-V, 100micrometer), an NMDA receptor antagonist, the acute effect of forskolin (10micrometer) was blocked. However, after washout of forskolin, an increase of corticostriatal EPSCs was still observed even in the presence of AP-V. When KT 5720 (5micrometer), a protein kinase A (PKA) inhibitor, was applied through the patch pipette, forskolin (10micrometer) increased corticostriatal EPSCs, but this increase was not maintained. When forskolin was applied together with AP-V and KT 5720, both the increase and maintenance of the corticostriatal EPSCs were blocked. These results suggest that forskolin activates both NMDA receptors and PKA, however, in a different manner.

Keyword

Striatum; Forskolin; PKA; NMD

MeSH Terms

Animals
Brain
Carbazoles
Cyclic AMP-Dependent Protein Kinases
Excitatory Postsynaptic Potentials
Forskolin
N-Methylaspartate
Patch-Clamp Techniques
Pyrroles
Rats
Receptors, N-Methyl-D-Aspartate
Synaptic Transmission
Carbazoles
Cyclic AMP-Dependent Protein Kinases
Forskolin
N-Methylaspartate
Pyrroles
Receptors, N-Methyl-D-Aspartate

Figure

• 

  Fig. 1. Forskolin enhances corticostriatal EPSCs in a dose dependent manner. (A) Plot of average EPSCs data shows that forskolin increases EPSCs amplitude (1 and 10 μM). The bar above the plotted graph indicates the period of drug application. (B) Forskolin increases EPSCs amplitude in a dose-dependent manner. Graph shows the average EPSCs change during forskolin treatment (early phase), and after its treatment (late phase) at each concentration. Note that the effect of 10 and 30 μM forskolin was maintained even after its washout. (C) Graph shows the average PPR change by forskolin. ∗p<0.05 when compared to baseline EPSCs.

• 

  Fig. 2. Early effect of forskolin needs NMDA receptor activation. (A) Plot of average EPSCs data shows that treatment of AP-V (100 μM), an NMDA receptor antagonist, blocks the early effect of forskolin (10 μM). However, after washout of forskolin, EPSCs still increase. The bar above the plotted graph indicates the period of drug application. Representative traces of EPSCs before (a), during (b), and after (c) forskolin treatment. (B) Column graph shows the average EPSCs data. ∗p<0.05 when compared to baseline EPSCs.

• 

  Fig. 3. Late enhancement of corticostriatal synaptic transmission by forskolin requires PKA activity. (A) Plot of average EPSCs data shows that intracellular application of KT 5720 (5 μM), a PKA inhibitor, does not affect the early increase by forskolin (10 μM), but blocks the late effect. The bar above the plotted graph indicates the period of drug application. Representative traces of EPSCs before (a), during (b), and after (c) forskolin treatment. (B) Column graph shows the average EPSCs data. ∗p<0.05 when compared to baseline EPSCs.

• 

  Fig. 4. Forskolin exerts no effect on corticostriatal synaptic transmission when both NMDA receptor and PKA activation are blocked. (A) Plot of average EPSCs data shows that the effect of forskolin (10 μM) on corticostriatal synaptic transmission was blocked when AP-V (100 μM) and KT 5720 (5 μM) were applied together. The bar above the plotted graph indicates the period of drug application. Representative traces of EPSCs before (a), during (b), and after (c) forskolin treatments. (B) Column graph shows the average EPSCs data.

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