Effects of subtype selective dopamine receptor agonists on progressive ratio responding for cocaine‐ and remifentanil‐paired stimuli

Abstract

Pretreatment with dopamine D3 receptor preferring agonists (e.g., pramipexole) has been shown to increase rats’ operant responding for stimuli previously paired with self‐administered cocaine. Presently, we assessed the ability of (1) agonists with different dopamine receptor preferences to increase responding for cocaine‐paired stimuli and (2) pramipexole to increase responding for opioid‐paired stimuli. Rats were trained to nose‐poke for IV infusions of cocaine or remifentanil under a progressive ratio (PR) schedule. Lights above the active manipulandum provided infusion‐paired conditioned stimuli (CS). Animals were then tested in extinction: nose‐poking produced the CS alone under the PR schedule, and a pretreatment of saline; pramipexole; the D2 preferring agonist, sumanirole; or the D1‐like agonist, SKF81297, was given before each session. Compared to saline, pramipexole and sumanirole, but not SKF81297, dose‐dependently increased responding for cocaine‐paired CS. Pramipexole also significantly increased responding for remifentanil‐paired CS. These increases depended on CS presentation: when the CS were also omitted from test sessions, pramipexole's effects were significantly attenuated. Thus, the response‐increasing effects of D2‐like agonists are not limited to D3 preferring compounds and cocaine‐paired CS. Funding: NIDA R01 DA024897 and R01 DA020669.