Reward without dopamine

Abstract

Dopamine (DA) is believed to play a fundamental role in reward processes. Virtually all drugs of abuse activate dopaminergic systems, as do "natural" rewards such as sexual interaction and food. Sweet-tasting solutions, for example, are a well characterized natural reward. In the present experiments, we used mice that cannot make DA (DD mice) to test the hypothesis that DA is necessary for reward. Sucrose preference, assessed with a computerized "lickometer," was used to determine whether DD mice respond preferentially for rewarding stimuli. DD mice preferentially chose sucrose over water, and also preferred the noncaloric sweetener saccharin. Furthermore, the rate of licking, bout size, and length were greater in DD mice drinking sweets than in controls. These data refute the necessity of DA for the reward processes manifested by sucrose preference. However, DD mice initiated licking less frequently than control mice and had fewer total licks. We suggest that DD mice have a deficit of goal-directed behavior that is not specific to reward processes. Lastly, juvenile DD mice demonstrate robust sucrose preference before experience with food in the presence of DA. Thus, DA is not required for mice to learn to consume sweet solutions preferentially. We conclude that DA is not required to find the sweet tastes of sucrose or saccharin rewarding.

Figure 1.

Preference for 0.5 m sucrose by WT and DD mice. A, Lickometer cage modified for mice. B, WT and DD mice were given the choice of either water or sucrose. Both WT (n = 3) and DD (n = 8) mice demonstrated significant preference. Asterisks denote preference (p < 0.01).

Figure 2.

DD mice did not increase locomotor behavior in response to repeated AMPH. A, DD mice (n = 12) were given l-dopa (50 mg/kg) at time 0, AMPH (2 mg/kg) at 24, 26, and 42 hr after l-dopa (filled arrowheads), and a control injection of PBS 44 hr after l-dopa (open arrowhead). The black bars indicate when room lights were off. The increased activity at 30 hr after l-dopa (white bar) is characteristic of DD mice (see Results). B, WT mice (n = 3) were treated as described for DD mice. C, Cumulative ambulations of WT (white columns) and DD (black columns) mice for 1.75 hr after AMPH or PBS at 24 (AMPH 1), 26 (AMPH 2), 42 (AMPH 3), and 44 (PBS 1) hr after l-dopa. ^*p < 0.05 compared with PBS value. D, DD and WT mice were given access to sucrose and water for 15 hr beginning 28 hr after the administration of l-dopa, either after AMPH at 24 and 26 hr (AMPH) or without previous AMPH administration (no AMPH). There was no difference in the total intake of DD or WT mice with or without previous AMPH administration.

Figure 3.

In the absence of releasable DA, DD mice preferred sweet solutions to water. WT (n = 7) and DD (n = 8) mice were given the choice of sucrose (black columns) or water (white columns). A, Both groups demonstrated significant preference for sucrose (p < 0.01). B, C, DD mice had fewer bouts (licking during consecutive 10 sec intervals) and fewer total licks at the sucrose tube compared with WT mice (p < 0.05). D-F, During each bout of sucrose intake, lick rate, bout length, and total licks/bout were greater for DD compared with WT mice (p < 0.01). G, H, Licking pattern of representative individual WT (G) or DD (H) mice given the choice of sucrose (filled circles) and water (open circles).

Figure 4.

Previous experience with DA was not required for sucrose preference by DD mice. Juvenile DD (n = 4) and WT littermates (n = 4) were given the choice of sucrose or water before their first injection of l-dopa. A, Both WT and DD juvenile mice preferred sucrose (p < 0.01). B, C, Licking pattern of representative individual WT (B) or DD (C) mice given the choice of sucrose (filled circles) or water (open circles). Juvenile DD mice demonstrated fewer total licks during the 18 hr test (mean total licks: WT, 2667 ± 855; DD, 438 ± 162).