Variations in nucleus accumbens dopamine associated with individual differences in maternal behavior in the rat

Abstract

Lactating rats exhibit stable individual differences in pup licking/grooming. We used in vivo voltammetry to monitor changes in extracellular dopamine (DA) in the nucleus accumbens (n. Acc) shell of lactating rats interacting with pups and found that (1) the DA signal increased significantly with pup licking/grooming; (2) the onset of such increases preceded pup licking/grooming; and (3) the magnitude and duration of the increase in the DA signal were significantly correlated with the duration of the licking/grooming bout. In females characterized on the basis of behavioral observations as high-licking/grooming mothers, the magnitude of the increase in the DA signal associated with licking/grooming was significantly greater than in low-licking/grooming dams. Dopamine transporter binding in the n. Acc was increased in low-compared with high-licking/grooming mothers. Injection of the selective DA uptake inhibitor GBR 12909 [1-(2-(Bis-(4-fluorophenyl)methoxy)ethyl)-4-(3 phenypropyl)piperazine dihydrochloride] (5 mg/kg, s.c.) increased the DA signal in the n. Acc and pup licking/grooming in low-licking/grooming mothers to levels comparable with those observed in high-licking/grooming dams. Receptor autoradiographic studies showed elevated levels of D1 and D3 receptors in the n. Acc shell region in high-licking/grooming dams. These results suggest that high- and low-licking/grooming dams differ in mesolimbic dopaminergic activity associated with mother-pup interactions. Such differences may serve as neural substrates for individual differences in the motivational component of maternal behavior.

Figure 1.

Mean ± SEM number of LG bouts (A) and duration (in minutes) of LG bouts (B) observed during the 6 hr testing sessions with high- and low-LG dams. High-LG dams engaged in more LG bouts (p < 0.05) and longer-duration LG bouts (p < 0.01) compared with low-LG dams.

Figure 2.

Schematic illustration of the sites of electrochemical probe placement of the six high- and six low-LG dams included in the electrochemical and behavioral analysis. All animals included in the analysis had confirmed probe placement in the nucleus accumbens shell.

Figure 3.

A, Representative illustrations of the change in nanomolar DA equivalent signal in the nucleus accumbens shell of high- and low-LG dams during bouts of licking/grooming. The gray bar indicates the duration of the LG bout (in minutes). B, Mean ± SEM increase in nanomolar DA equivalent signal associated with licking/grooming bouts in high- and low-LG dams. High-LG dams had higher increases in DA signal at the start of the LG bout (p < 0.05), and peak increases during the bout were also elevated in high-LG compared with low-LG dams (p < 0.01). No group differences in DA signal were observed at the end of the LG bout or 30 sec after the termination of the LG bout.

Figure 4.

A, Mean ± SEM duration (in minutes) of the increase in nanomolar DA equivalent signal during LG bouts in high- and low-LG dams. The duration of increase in DA signal was significantly longer in high-LG compared with low-LG dams (p < 0.05). B, Scattergram illustrating the correlation between duration of LG bout and duration of the corresponding increases in DA signal. A highly significant positive correlation was found between the duration of LG and the duration of the DA increase (r = 0.98; p < 0.001).

Figure 5.

Scattergram illustrating the correlation between duration (in minutes) of a licking/grooming bout and the magnitude of the peak change in nanomolar DA equivalent signal associated with the bout (r = 0.80; p < 0.001).

Figure 6.

A, Mean ± SEM time (in minutes) spent licking/grooming by high- and low-LG dams (n = 3 per group) given subcutaneous injection of saline or GBR 12909 (5 mg/kg). GBR 12909 abolished group differences in licking/grooming. Treatment with GBR 12909 resulted in increased LG in low-LG dams (p < 0.01). B, Mean ± SEM change in nanomolar DA equivalent signal in the n. Acc of high- and low-LG dams during LG bouts after drug or saline treatment. Injection of GBR 12909 1 hr before the observation session resulted in an increase in DA signal (p < 0.05) compared with saline treatment.

Figure 7.

Changes in nanomolar DA equivalent signal in a high-LG dam and a low-LG dam (nontreated) associated with the brief (1 min) removal of pups from the testing apparatus. The first arrow (open bar) indicates the time of removal of pups, and the second arrow (filled bar) indicates the time of return of pups to the testing apparatus.

Figure 8.

Changes in nanomolar DA equivalent signal in a high-LG dam (A) and a low-LG dam (B) after the brief (1 min) removal of pups from the testing apparatus. The first arrow (open bar) indicates the time of removal of pups, and the second arrow (filled bar) indicates time of return of pups to the testing apparatus. C, Mean ± SEM change in nanomolar DA equivalent signal in the n. Acc of high- and low-LG dams after the brief (1 min) removal of pups from the testing apparatus. Injection of GBR 12909 2 hr before testing resulted in an increase in DA signal (p < 0.05), whereas injection of quinpirole resulted in a decrease in DA signal (p < 0.05) compared with saline treatment.

Figure 9.

Mean ± SEM DA receptor binding (femtomoles per milligram) in the nucleus accumbens core (A) and shell (B) of high- and low-LG lactating dams. D₁ (p < 0.05) and D₃ (p < 0.001) receptor binding was elevated in the n. Acc shell of high-compared with low-LG dams. No group differences were found in DA receptor binding in the n. Acc core region. Overall, D₃ receptor binding was elevated in the shell compared with the core (p < 0.001).

Figure 10.

Representative photomicrographs of DA receptor and transporter binding in the nucleus accumbens of high- and low-LG lactating dams.