Aim: 

Aim of the study was to investigate whether and how cAMP affects the resting membrane potential of medium spiny neurons (MSNs) in the nucleus accumbens (NAc).

Methods: 

Application of the adenylyl cyclase stimulator forskolin (FSK, 20 mM) to NAc slices elicited membrane depolarizations of 4.1±0.7 mV. In voltage-clamp FSK induced inward currents of -17.8±1.7 pA.

Results: 

Similar results were obtained by applying the cAMP analogue 0.5 mM dB-cAMP or intracellularly applying 1 mM cAMP. FSK and dB-cAMP-induced effects were unaffected by PKA, PKC or PLC activity suggesting a direct action of cAMP on ion channels. Furthermore FSK- and dB-cAMP-effects were associated to increased membrane input resistance, suggesting that inhibition of ion conductances underlies the cAMP's effects. Voltage-clamp experiments showed that FSK effects are due to inhibition of inward-rectifier K⁺ channels (Kir) because: i) they were never observed when Cs⁺ was present in the pipette solution; ii) they were abolished by BaCl₂; iii) Kir currents elicited by hyperpolarizing voltage protocols were decreased by FSK; iv) net current inhibited by FSK showed inward rectification at hyperpolarized potentials and reversal potential of -89.3±1.2 mV, which shifted concurrently with extracellular K⁺ concentrations. Inhibition of Kir currents was also elicited by neurotransmitters coupled to cAMP signaling such as dopamine and noradrenaline.

Conclusion: 

cAMP excitatory effects may facilitate MSN transition from quiescent downstate to upstate.