Extinction of Heroin Seeking Does Not Require the Infralimbic Cortex or Its Projections to the Nucleus Accumbens Shell or Amygdala

Abstract

Evidence indicates that the activity of the infralimbic cortex (IL), as well as its projections to the nucleus accumbens shell (NAshell) and amygdala, following an unreinforced lever press is critical for cocaine extinction learning and retention. It is unclear whether the same neural circuitry is involved in extinction encoding for other classes of addictive drugs, including opioids. In this study, we used a behaviour-controlled optogenetic approach in female and male Sprague–Dawley rats to examine the role of the IL and its projections in the extinction of heroin seeking. Rats first underwent 12+ days of 6- or 3-h heroin self-administration sessions, followed by 12 days of extinction training. Optogenetic inhibition of the IL, IL-NAshell or IL-amygdala pathway was given for 20 s immediately following an unreinforced lever press during the first 5 days of extinction. Unlike cocaine extinction, these manipulations had no effect on lever pressing during extinction training, nor on the retention of extinction learning, as assessed during the subsequent 7 days of extinction without optogenetic inhibition. These results suggest that the extinction of heroin seeking does not involve the same infralimbic mechanisms that are critical for the extinction of cocaine seeking. Although extinction learning did not differ by sex, analyses of self-administration data revealed that females self-administered more heroin than males in 3 h, but not 6 h, self-administration sessions, indicating session length-dependent sex differences in heroin taking.