Environmental enrichment facilitates electric barrier induced heroin abstinence after incubation of craving in male and female rats

Abstract

Background: Treatment strategies that aim to promote abstinence to heroin use and reduce vulnerability to drug-use resumption are limited in sustainability and long-term efficacy. We have previously shown that environmental enrichment (EE), when implemented after drug self-administration, reduces drug-seeking and promotes abstinence to cocaine and heroin in male rats. Here, we tested the effects of EE on abstinence in an animal conflict model in males and females, and after periods where incubation of craving may occur.

Methods: Male and female rats were trained to self-administer heroin followed by 3 or 21 days of a no-event-interval (NEI). Following NEI, rats were permanently moved to environmental enrichment (EE) or new standard (nEE) housing 3 days prior to resuming self-administration in the presence of an electric barrier adjacent to the drug access lever. Electric barrier current was increased daily until rats ceased self-administration.

Results: We found that 21 days of NEI led to significantly greater heroin self-administration and a trend toward shorter latencies to emit the first active lever press in the first abstinence session compared to 3 days of NEI. EE, when compared to nEE, led to longer latencies in the first abstinence session. Also, EE groups of both sexes and in both NEIs achieved abstinence criteria in significantly fewer numbers of sessions.

Conclusions: EE facilitates abstinence in males and females and after periods where incubation of craving may occur. This suggests that EE may benefit individuals attempting to abstain from heroin use and may aid in the development of long term treatment strategies.

Keywords: Abstinence; Conflict model; Environmental enrichment; Heroin addiction; Incubation of craving; Self-administration.

Figure 1.

Heroin self-administration. Mean (+SEM) number of infusions (1A), active (1B) and inactive (1C) lever presses across 15 heroin self-administration sessions in males (black) and females (gray) prior to housing and NEI

Figure 2.

The effects of EE and the initial electric barrier on heroin self-administration after 3 and 21 days of NEI. (A) Mean (+SEM) number of infusions (top), active lever (middle), and inactive lever (bottom) presses during the first 30 minutes of the last heroin-self administration session (FR1; before NEI and housing) and first electric barrier session (EBA; after NEI and housing) in males (black) and females (gray) that were subject to 3 (circles) or 21 (triangles) days of NEI and 3 days of nEE (left) or EE (right). * represents significantly less infusions (p < .05) in rats housed in EE, but not nEE, during the first electric barrier session when compared to the last FR1 session, regardless of sex and NEI. (B) Indivudal and mean (+SEM) latencies (seconds) to the first active lever press during the first electric barrier session in males (black) and females (gray) after 3 (solid bars) or 21 (striped bars) days of NEI in rats housed in nEE (left) and EE (right). * represents significantly longer latencies in rats housed in EE when compared to nEE, irrespective of NEI and sex. Rats that did not press on the first day were assigned a latency of 1800s and included in the anlysis (data not shown here).

Figure 3.

The effects of EE on electric barrier induced abstinence. (A) Individual and mean (+SEM) sessions to achieve EBA criteria in males (black) and females (gray) after 3 (solid bars) or 21 (striped bars) days of NEI and housed in nEE (left) or EE (right). * represents significantly (p <.05) less sessions required to cease heroin self-administration in EE rats when compared to nEE, irrespective of NEI and sex. (B) Individual and mean (+SEM) current (mA) at which rats ceased heroin self-administration. * represents significantly lower (p < .05) currents in rats housed in EE when compared to nEE.

Figure 4.

The effects of cessation of drug intake and EE on nociception. Figure represents individual and mean (+SEM) tail-flick latencies 1 day after heroin self-administration (Baseline), 21 days after the last IVSA session (21 NEI) and 1 day after EBA criteria were met (EBA) in males (black) and females (gray). Following measurements after 21 NEI, rats were housed in nEE or EE for 3 days followed by daily abstinence sessions.