Blockade of the acquisition, but not expression, of associative learning by pre-session intra-amygdala R(+) 7-OH-DPAT

RATIONALE: Two issues were addressed regarding the effects of amygdala dopamine manipulations on associative learning: first, an apparent contradiction between the effects of post- vs. pre-session dopaminergic manipulations and second, the ability of dopaminergic infusions to affect association formation vs. its expression following extended training.

OBJECTIVES: The ability of pre-session infusions of a dopamine receptor agonist (R(+) 7-OH-DPAT) to inhibit acquisition of a conditioned approach response was examined and compared with the same manipulation following overtraining. Further experiments extended these findings.

MATERIALS AND METHODS: Experiment 1 infused pre-session intra-amygdala R(+) 7-OH-DPAT (0, 0.1, 1 nmol) during conditioned approach acquisition. Experiment 2 applied pre-session intra-amygdala R(+) 7-OH-DPAT (0, 0.01, 0.1, 1 nmol) during expression of the same response, once well learned. Experiment 3 required the inhibition of a conditioned approach response following unconditioned stimulus (US) removal. Experiment 4 examined the ability of animals with prior drug experience to acquire a conditioned response to a novel stimulus.

RESULTS: Experiments 1-3 showed that pre-session amygdala R(+) 7-OH-DPAT impaired acquisition of either excitatory or inhibitory conditioned responding, but was ineffective following overtraining. Drug-induced impairments in acquisition of a specific conditioned stimulus (CS)-US relationship continued well beyond the cessation of drug treatment, but were found not to transfer to an alternate CS in Experiment 4.

CONCLUSIONS: Pre-session dopamine receptor activation within the amygdala may impair the acquisition, but not expression, of CS-US associations. Enhanced learning reported earlier following post-session dopamine receptor activation may occur indirectly through reduced interference with the consolidation of recent learning.