Instrumental learning, but not performance, requires dopamine D1-receptor activation in the amygdala

Abstract

Substantial experimental evidence exists suggesting a critical role for dopamine in reinforcer-related processes, such as learning and drug addiction. Dopamine receptors, and in particular D1 receptors, are widely considered as modulators of synaptic plasticity. The amygdala contains both dopamine terminals and dopamine D1 receptors and is intimately involved in motivation and learning. However, little is known about the involvement of D1 receptor activation in two subnuclei of the mammalian amygdala, the central nucleus and basolateral complex in instrumental learning. Following recovery from surgery and preliminary training, rats with bilateral indwelling cannulae aimed at the central nucleus or basolateral complex were trained to lever-press for sucrose pellets over 12 sessions. Infusion of the selective D1 antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (0.3 nmol and 3.0 nmol) prior to the first five training sessions dose-dependently impaired instrumental learning when compared with vehicle-infused controls. All rats were then exposed to five sessions drug-free; lever-pressing quickly reached equal levels across groups. A drug infusion prior to an 11th session revealed no effect on performance. Control experiments indicated that basic motivational processes and general motor responses were intact, such as spontaneous feeding and locomotor activity. These results show an essential role for D1-receptor activation in both the central nucleus and basolateral complex on the acquisition of lever pressing for sucrose pellets in rats, but not the performance of the behavior once conditioned. We propose that instrumental learning is dependent on plasticity in the central nucleus and basolateral complex amygdala, and that D1 receptor activation participates in transcriptional processes that underlie this plasticity.

Fig. 1

Histological reconstructions of cannula placements in rats in the instrumental learning experiments. Histological sections were examined under light microscope and the site of infusion was estimated. Placements in the CeA are represented in schematic form in A, while placements in the BLA are represented in B. Symbols are consistent with other figures; black circles are vehicle treated (CeA: n=7 and BLA: n=8), light gray diamonds represent 0.3 nmol SCH-23390 treated (n=7 and n=7) and dark gray diamonds represent 3.0 nmol SCH-23390 treated (n=7 and n=7). The schematic reconstructions show that there was no systematic bias in placement based on group assignment. Note that CeA placements were anterior to the BLA placements. Two examples of Cresyl Violet-stained pictomicrographs are shown in C (CeA) and D (BLA). Placements in the CeA for the locomotor portion of experiment 1 were consistent with those in panel A. The vehicle-treated rats in the instrumental learning portion of experiment 2 were used in the locomotor and feeding control portion. Schematic diagrams are from The Rat Brain in Stereotaxic Coordinates. (4th ed.) (Paxinos and Watson, 1998).

Fig. 2

Effects of infusions the D1 antagonist SCH-23390 in the CeA on instrumental learning, performance and nosepoking. Rats received infusions of SCH-23390 or vehicle prior to sessions 1–5, and prior to session 11, but not prior to sessions 6–10. (A) Mean number of LP per session per group for sucrose pellets (±S.E.M.). * P<0.05 main effect of treatment. (B) Mean number of NP per session per group (±S.E.M.). No statistical reliable main effect of treatment or interaction on nosepoking was found.

Fig. 3

Effects of infusions the D1 antagonist SCH-23390 in the BLA on instrumental learning, performance and nosepoking. Rats received infusions of SCH-23390 or vehicle prior to sessions 1–5, and prior to session 11, but not prior to sessions 6–10 or session 12. (A) Mean number of LP per session per group for sucrose pellets (±S.E.M.). * P<0.05 different from vehicle (Tukey HSD). (B) Mean number of NP per session per group (±S.E.M.). * P<0.05 different from vehicle.

Fig. 4

Microstructural behavioral analysis of D1 antagonism in the CeA and the basolateral amygdala (BLA). Panels A and B show the conditional probability of a NP given a Reinf was the last recorded event (Pr(NP Reinf)) in the CeA and BLA. Panels C and D shows the average latency of a NP following a Reinf. Note that during session 3, in the CeA, only one 3.0 nmol-treated rat (the dark diamond) earned enough Reinf (i.e. more than five) to meet the criteria for computing a mean latency (see method for description of computations).