Differential effects of 5-HT(2A) and 5-HT(2C) receptor blockade on strategy-switching

Abstract

Recent experiments indicate that blockade of serotonin (5-HT) 2A and 2C receptors have differential effects on reversal learning. The present experiments investigated the effects of the 5-HT(2A) receptor antagonist, ketanserin and 5-HT(2C) receptor antagonist, SB242084 on acquisition and strategy-switching in a visual cue-response paradigm. Long-Evans rats were trained in a cross-maze to enter an arm based on color (visual cue version) or a specific turn response (response version). Systemic treatment with ketanserin did not affect initial learning of a visual cue or response discrimination, but ketanserin at 0.5 mg/kg significantly enhanced a switch between visual cue and response strategies. Ketanserin facilitated strategy-switching by inhibiting responses to a previously relevant strategy without affecting choices to never-reinforced strategies. Treatment with SB242084 (0.5, 1.0 or 2.0 mg/kg) did not affect acquisition of a visual cue or response discrimination. SB242084 treatment also did not affect strategy-switching. The present findings suggest that blockade of 5-HT(2A), but not 5-HT(2C), receptors enhance strategy switching.

Figure 1

The effect of ketanserin treatment on visual cue acquisition and switch to response. Each rat received an intraperitoneal injection of vehicle (Veh) or one of two doses of ketanserin (Ket) during the acquisition phase or the switch phase 30 minutes prior to testing. The treatments in the legends represent the treatment received prior to acquisition (1^st) followed by the treatment received prior to the switch phase (2^nd). Treatment given prior to acquisition or the switch phases in bold type. A) Mean (± SEM) trials to criterion on acquisition of a visual cue discrimination. Injection of ketanserin had no effect on acquisition. B) Mean (± SEM) trials to criterion on a switch to a response strategy. Ketanserin at 0.5 mg/kg dose facilitated a switch to a response strategy. * = P < .05 vs. Veh – Veh, Ket 0.5 mg/kg – Veh, Veh – Ket 0.05 mg/kg. C) Mean (± SEM) errors committed by type during the switch to a response strategy. Ketanserin 0.5 mg/kg administered prior to the acquisition phase of testing resulted in an increase in perseverative responding during the switch phase. * = P < .05 vs. Veh – Veh, Veh – Ket 0.05 mg/kg, Veh – Ket 0.5 mg/kg. Ketanserin 0.5 mg/kg administered prior to the switch to response significantly reduced regressive errors. * = P < .05 vs. Veh – Veh, Ket 0.5 mg/kg – Veh, Veh – Ket 0.05 mg/kg. There was no significant group difference in the number of never-reinforced errors committed.

Figure 2

The effect of ketanserin treatment on response acquisition and switch to visual cue. Each rat received an intraperitoneal injection of vehicle (Veh) or one of two doses of ketanserin (Ket) during either the acquisition or the switch phase 30 minutes prior to testing. The treatments in the legends represent the treatment received prior to acquisition (1^st) followed by the treatment received prior to the switch phase (2^nd). Treatment given prior to either acquisition or the switch phase is in bold type. A) Mean (± SEM) trials to criterion on acquisition of a response strategy. Injection of ketanserin had no effect on acquisition trials to criterion. B) Mean (± SEM) trials to criterion on switch to a visual cue discrimination. Ketanserin at 0.5 mg/kg dose facilitated the switch to a response strategy. * = P < .05 vs. Veh – Veh, Ket 0.5 mg/kg – Veh, Veh – Ket 0.05 mg/kg. C) Mean (± SEM) errors committed by type during the switch to a visual cue discrimination. Ketanserin 0.5 mg/kg administered prior to the acquisition phase of testing resulted in an increase in perseverative responding during the switch phase. * = P < .05 vs. Veh – Ket 0.5 mg/kg. Ketanserin 0.5 mg/kg administered prior to the switch to visual cue significantly reduced regressive errors.* = P < .05 vs. Veh – Veh, Ket 0.5 mg/kg – Veh, Veh – Ket 0.05 mg/kg. There was no significant difference among the groups in never-reinforced errors.

Figure 3

The effect of ketanserin treatment on visual cue acquisition and switch to response. Each rat received an intraperitoneal injection of vehicle (Veh) or ketanserin 0.5 mg/kg (Ket) during both the acquisition phase and the switch phase 30 minutes prior to testing. The treatments in the legends represent the treatment received prior to acquisition (1^st) followed by the treatment received prior to the switch phase (2^nd). Treatment given prior to acquisition or the switch phases in bold type. A) Mean (± SEM) trials to criterion on acquisition of a visual cue discrimination. Injection of ketanserin had no effect on acquisition. B) Mean (± SEM) trials to criterion on switch to a response strategy. Ketanserin 0.5 mg/kg facilitated a switch to a response strategy. ** = P < 0.01 vs. Veh – Veh. C) Mean (± SEM) errors committed by type during the switch to a response strategy. There were trends for a reduction in both perseverative and regressive errors (Ket 0.5 mg/kg – Ket 0.5 mg/kg group vs. the Veh – Veh, P = 0.10 for both error types). There was no significant group difference in the number of never-reinforced errors committed.

Figure 4

The effect of prazosin treatment on switch from visual cue to response strategy. Each rat received an intraperitoneal injection of vehicle (Veh) or one of two doses of prazosin (Prz) during either the acquisition or the switch phase 30 minutes prior to testing. The treatments in the legends represent the treatment received prior to acquisition (1^st) followed by the treatment received prior to the switch phase (2^nd). Treatment administered in a specific test phase is in bold type. A) Mean (± SEM) trials to criterion on acquisition of a visual cue discrimination. All vehicle treated groups achieved acquisition criterion in a similar manner. B) Mean (± SEM) trials to criterion during the switch to a response strategy. Injection of prazosin had no effect on the switch to response.

Figure 5

The effect of SB242084 on visual cue acquisition and switch to response. Each rat received an intraperitoneal injection of Vehicle (Veh) or SB242084 (SB) during the acquisition or switch phase, 30 minutes prior to testing. The treatments in the legends represent the treatment received prior to acquisition (1^st) followed by the treatment received prior to the switch phase (2^nd). The treatment administered prior to each test phase is in bold type. A) Mean (± SEM) trials to criterion on acquisition of a visual cue discrimination. Injection of SB242084 had no effect on visual cue acquisition. B) Mean (± SEM) trials to criterion during the switch to a response strategy. Injection of SB242084 had no effect on the switch to response.

Figure 6

The effect of SB242084 on response acquisition and switch to visual cue. Each rat received an intraperitoneal injection of vehicle (Veh) or SB242084 (SB) during either the acquisition or the switch phase, 30 minutes prior to testing. The treatments in the legends represent the treatment received prior to acquisition (1^st) followed by the treatment received prior to the switch phase (2^nd). The treatment administered prior to a test phase is in bold type. A) Mean (± SEM) trials to criterion on acquisition of response strategy. Injection of SB242084 had no effect on response acquisition. B) Mean (± SEM) trials to criterion during the switch to a visual cue discrimination. Injection of SB242084 had no effect on the switch to visual cue.