D2 dopamine modulation of corticoaccumbens synaptic responses changes during adolescence

Abstract

Dopaminergic afferents from the ventral tegmental area (VTA) modulate information processing in the nucleus accumbens (NA), a brain region critical for motivation and reward mechanisms. In NA medium spiny neurons (MSNs) from young rats, D(2) agonists have been shown to decrease the amplitude of corticoaccumbens synaptic responses. As several dopamine-related functions change during adolescence, we assessed the D(2) modulation of cortical inputs with whole-cell recordings in slices obtained from adult and preadolescent rats. The D(2) agonist quinpirole (5 microM) decreased synaptic response of NA MSNs to electrical cortical stimulation in slices from preadolescent rats. In slices from adult rats, however, quinpirole increased both the amplitude of evoked synaptic responses and the frequency of spontaneous synaptic events. These effects were blocked by the GABA-A antagonist picrotoxin (50 microM), revealing a D(2)-mediated decrease These results suggest that D(2) receptors modulate NA neurons differently in young and adult rats, due to the emergence of a D(2)-facilitated GABA component in corticoaccumbens responses during adolescence.

Fig. 1

Basic membrane properties of preadolescent and adult MSNs recorded in the NA. Traces show overlays of whole-cell current-clamp responses to depolarizing and hyperpolarizing current pulses (50-pA steps from −200 to +300 pA, 500 ms duration) in (A) preadolescent and (B) adult rats. Arrows point to the ramp depolarization preceding spikes in both age groups. Bottom left on both panels: I/V plots revealing an inward rectification with depolarizing current pulses, which corresponds to the ramp depolarization indicated by the arrow. Bottom right on both panels: DAB staining of representative MSNs filled with Neurobiotin during recording. Calibration bars, 50 μm.

Fig. 2

EPSPs evoked by electrical stimulation of the white matter adjacent to the NA and carrying cortical fibers in preadolescent and adult rats. (A) Tyrosine hydroxylase-stained slice illustrating the position of recording and stimulating electrodes. Inset shows an IR-DIC image of a MSN in the NA (arrow). (B) Representative corticoaccumbens EPSP in a slice from a preadolescent rat showing an overlay of EPSP evoked before (baseline) and after CNQX (10 μM). Traces are average of five repetitions. (C) Population data of EPSP amplitude normalized to baseline levels. Values are averages per minute. (D) Overlay of representative corticoaccumbens EPSPs in a slice from an adult rat showing blockade with CNQX. (E) Time course of normalized EPSP amplitudes for all the neurons tested. Calibration bar, 25 μm.

Fig. 3

Dose-dependent effects of a D₂ agonist on corticoaccumbens responses are different in young and adult slices. (A) Examples of corticoaccumbens EPSPs following exposure to different concentrations of quinpirole at 10-min intervals in a representative MSN from a preadolescent rat. Each trace is an average of five repetitions. (B) Representative EPSP with increasing quinpirole concentrations in an MSN from an adult rat. (C) Plot indicating average EPSP amplitude for each concentration of quinpirole in preadolescent rats (mean ± SD). (D) Plot of EPSP amplitude after quinpirole in adult rats. *P < 0.02.

Fig. 4

D₂ modulation of EPSPs. (A) Representative traces of cortico-NA EPSPs before (baseline) and after changing the bath to ACSF (top) or quinpirole (bottom) in slices from preadolescent rats. Each trace is the average of 10 repetitions. The graph to the right plots normalized EPSP amplitude after changing the bath to ACSF (open circles), quinpirole (black circles) or a cocktail of the selective D₂ antagonist eticlopride and quinpirole (grey circles). Values are averages per minute. (B) Representative traces of cortico-NA EPSPs and normalized EPSP amplitude plot in slices from adult rats.

Fig. 5

GABA-A component in the D₂ modulation of corticoaccumbens EPSPs. (A) Representative traces of corticoaccumbens EPSPs before and after changing the bath to picrotoxin (top) or picrotoxin + quinpirole (bottom) in slices from preadolescent rats. Each trace is an average of 10 repetitions. The graph to the right shows normalized EPSP amplitude for each treatment. Values are averages per minute. (B) Similar display of EPSP amplitude and normalized plots obtained with slices from adult rats.

Fig. 6

Spontaneous depolarizing potentials in slices from adult and preadolescent rats. (A) Representative traces of spontaneous dPSPs before and after changing the bath to ACSF (top) or quinpirole (bottom) in slices from preadolescent rats. (B) Similar display of representative traces obtained in slices from adult rats. (C) Bar graph showing normalized frequency of spontaneous dPSP in adult and preadolescent rats after ACSF or quinpirole treatment.

Fig. 7

Effect of D₂ activation on spontaneous inward currents recorded in voltage-clamp at −70 mV. (A) Representative traces of spontaneous inward current events before and after changing the bath to ACSF (top), CNQX (middle) and CNQX + quinpirole (bottom) in slices from preadolescent rats. (B) Representative traces of spontaneous inward currents with similar treatments in slices from adult rats. (C) Representative traces of spontaneous inward currents after changing the bath to ACSF (top), CNQX + quinpirole (middle) and CNQX + quinpirole + picrotoxin (bottom) in slices from adult rats. (D) Bar graph depicting the frequency of spontaneous inward current events in slices from preadolescent and adult rats for each treatment.