Increasing the number of extinction sessions suppresses context-specific sensitization in mice.

Abstract

The present experiment examined the effects of the number of conditioned stimulus sessions on (a) the rate of extinction of conditioned hyperactivity and (b) the subsequent expression of context-specific sensitization in mice. Male, Swiss Webster mice (n = 10/group) received methamphetamine (0.5 mg/kg) associated with locomotor activity chambers (paired) or home cages (unpaired) for five sessions (acquisition) followed by vehicle injections (saline) for either 5 (1 session/day × 5 days) or 20 (2 sessions/day × 10 days) sessions (extinction). All mice received an escalating methamphetamine-dose regimen (0.25-1.0 mg/kg, 1 dose/day for 3 days) regimen 24 h after the last extinction session (tests for context-specific sensitization). Distance traveled and vertical counts assessed locomotor activity. Both measures of locomotor activity detected between-session sensitization; however, the distance traveled measure was more sensitive in detecting conditioned hyperactivity. The vertical counts, but not the distance traveled measure, found that 5 extinction sessions compared with 20 extinction sessions produced slower extinction, perhaps owing to the trial spacing effect. However, the distance traveled measure revealed that 20, but not 5, extinction sessions completely suppressed context-specific sensitization following the 0.25 mg/kg methamphetamine challenge dose. These results suggest that increasing the number of conditioned stimulus sessions during extinction effectively suppresses the expression of context-specific sensitization, lending support to a 'Pavlovian excitatory conditioning hypothesis' of context-specific sensitization.