Systemic administration of 8-OH-DPAT and eticlopride, but not SCH23390, alters loss-chasing behavior in the rat

Abstract

Gambling to recover losses is a common gaming behavior. In a clinical context, however, this phenomenon mediates the relationship between diminished control over gambling and the adverse socioeconomic consequences of gambling problems. Modeling loss-chasing through analogous behaviors in rats could facilitate its pharmacological investigation as a potential therapeutic target. Here, rats were trained to make operant responses that produced both food rewards, and unpredictably, imminent time-out periods in which rewards would be unavailable. At these decision points, rats were offered choices between waiting for these time-out periods to elapse before resuming responding for rewards ('quit' responses), or selecting risky options with a 0.5 probability of avoiding the time-outs altogether and a 0.5 probability of time-out periods twice as long as signaled originally ('chase' responses). Chasing behavior, and the latencies to chase or quit, during sequences of unfavorable outcomes were tested following systemic administration of the 5-HT1A receptor agonist, 8-OH-DPAT, the D2 receptor antagonist, eticlopride, and the D1 receptor antagonist, SCH23390. 8-OH-DPAT and eticlopride significantly reduced the proportion of chase responses, and the mean number of consecutive chase responses, in a dose-dependent manner. 8-OH-DPAT also increased latencies to chase. Increasing doses of eticlopride first speeded, then slowed, latencies to quit while SCH23390 had no significant effects on any measure. Research is needed to identify the precise cognitive mechanisms mediating these kinds of risky choices in rats. However, our data provide the first experimental demonstration that 5-HT1A and D2, but not D1, receptor activity influence a behavioral analog of loss-chasing in rats.

Figure 1

Stimulus configurations for the choices in the loss-chasing task as implemented in 8 standard 5-hole operant chambers and performed following full training (see Supplementary Information). On ‘partially reinforced' (PR) trials (70% of the total), nose-poke responses in hole 5 produced food rewards. During ‘chasing episodes', the light in hole 5 flashed (0.5 Hz) and holes 1 and 3 were illuminated to indicate choice-points involving nose-poke responses in hole 3 that yielded fixed time-out periods of 4 s (‘quit' responses) or nose-poke responses in hole 1 that yielded no time-out periods or time-out periods of 8 s with probabilities of 0.5 (1st ‘chase'). Following losing chase responses, the light in hole 1 flashed (0.5 Hz) and holes 2 and 3 were illuminated to indicate further choice-points involving nose-poke responses in hole 3 (‘quit' responses) that yielded fixed time-outs of 8 s or nose-poke responses in hole 2 that yielded no time-out at all or time-out periods of 16 s, again with the probabilities of 0.5 (2nd ‘chase'). For 12 of the 24 rats, the 1st and 2nd chase responses were allocated to holes 1 and 2, as described above. For the remaining rats, the allocations were swapped so that the 1st and 2nd chase responses were allocated to hole 2 and hole 1, respectively. At every choice-point, the expected value in terms of the ‘opportunity cost' of quit responses (4 or 8 s) and chase response (0.5 × 8 s and 0.5 × 16 s) were equal, indicating no actual time advantage for either behavioral strategy.

Figure 2

Mean proportion of ‘chase' against ‘quit' responses made by 18 rats while performing the loss-chasing task following three drug treatments: the 5-HT_1A receptor agonist 8-OH-DPAT (saline, 0.1, 0.3, and 0.6 mg/kg), the D₂ receptor antagonist eticlopride (saline, 0.01, 0.03, and 0.06 mg/kg), and the D₁ receptor antagonist SCH23390 (saline, 0.001, 0.003, and 0.01 mg/kg). Dashed line represents perfectly balanced chase and quit responding.

Figure 3

Mean number of consecutive ‘chase' responses per chasing episode in 18 rats while performing the loss-chasing task following three drug treatments: the 5-HT_1A receptor agonist 8-OH-DPAT (saline, 0.1, 0.3, and 0.6 mg/kg), the D₂ receptor antagonist eticlopride (saline, 0.01, 0.03, and 0.06 mg/kg), and the D₁ receptor antagonist SCH23390 (saline, 0.001, 0.003, and 0.01 mg/kg).

Figure 4

Mean latencies for ‘chase' responses made by 18 rats while performing the loss-chasing task following three drug treatments: the 5-HT_1A agonist 8-OH-DPAT (saline, 0.1, 0.3, and 0.6 mg/kg), the D₂ receptor antagonist eticlopride (saline, 0.01, 0.03, and 0.06 mg/kg), and the D₁ receptor antagonist SCH23390 (saline, 0.001, 0.003, and 0.01 mg/kg).

Figure 5

Mean latencies for ‘quit' responses made by 18 rats while performing the loss-chasing task following three drug treatments: the 5-HT_1A agonist 8-OH-DPAT (saline, 0.1, 0.3, and 0.6 mg/kg), the D₂ receptor antagonist eticlopride (saline, 0.01, 0.03, and 0.06 mg/kg), and the D₁ receptor antagonist SCH23390 (saline, 0.001, 0.003, and 0.01 mg/kg).