Environmental enrichment protects against the acquisition of cocaine self-administration in adult male rats, but does not eliminate avoidance of a drug-associated saccharin cue

Abstract

One of the most menacing consequences of drug addiction is the devaluation of natural rewards (e.g. food, sex, work, money, caring for one's offspring). However, evidence also suggests that natural rewards, such as an enriched environment, can devalue drugs of abuse. Thus, this study used a rodent model to test whether exposure to an enriched environment could protect adult rats from acquiring cocaine self-administration and from the resultant drug-induced devaluation of a natural saccharin reward cue. Adult male Sprague-Dawley rats were implanted with intravenous jugular catheters. Rats were then separated into two housing conditions: an enriched condition, including social companions(four/cage) and novel objects (e.g. balls, polyethylene tubes, paper, etc.), and a nonenriched condition where the rats were singly housed with no novel objects. During testing, the rats were given 5-min access to 0.15% saccharin, followed by 1 h to self-administer saline or cocaine (0.167 mg/infusion) on fixed ratio and progressive ratio schedules of reinforcement. The results showed that rats that were singly housed in the nonenriched environment fell into two groups: low drug-takers (n=34) and high drug-takers (n=12). In comparison, only one out of the 22 rats housed in the enriched environment was a high drug-taker. Thus, all rats in the enriched environment, except one, behaved like low drug-takers under the nonenriched condition. As such, these rats self-administered almost no drug on either the fixed ratio or the progressive ratio schedule of reinforcement and were extremely slow to self-administer their first cocaine infusion. Interestingly, despite their very low levels of drug self-administration, low-drug-taking rats housed in the enriched environment continued to avoid intake of the drug-associated saccharin cue. Taken together, these data suggest that the enriched environment itself served as a salient natural reward that reduced cocaine seeking and cocaine taking, but had little impact on avoidance of the cocaine-paired taste cue. The protective effects of the enriched environment were robust and, as such, have important implications for the methods used in the study of drug addiction in animal models and for the prevention, and possibly the treatment, of the disease in adult humans.

Figure 1

Timeline of behavioral training and experimental testing. Days postnatal (PN) are indicated at the beginning of each manipulation.

Figure 2

Mean (+/- SEM) number of infusions self-administered/60 min. Left panel. Mean (+/- SEM) number of infusions self-administered across trials by rats housed in the non-enriched environment (Non-EE) in the saccharin-saline (white circles), saccharin-cocaine low (black circles), or saccharin-cocaine high (black triangles) condition. * denotes statistical significance (ps < 0.01) compared to Non-EE saccharin-cocaine low and # denotes statistical significance (p < 0.01) compared to Non-EE saccharin-saline. Right panel. Mean (+/- SEM) number of infusions self-administered across trials by rats housed in the enriched environment (EE) in the saccharin-saline (white circles), saccharin-cocaine low (black circles), or saccharin-cocaine high (black triangles) condition.

Figure 3

Left panel. Mean (+/- SEM) terminal (trials 13-14) number of cocaine infusions self-administered by rats housed in the non-enriched environment (Non-EE) in the saccharin-saline (white bar), saccharin-cocaine low (light gray bar), or saccharin-cocaine high (dark gray bar) condition. * denotes statistical significance (p < 0.01) compared to Non-EE saccharin-cocaine low and Non-EE saccharin-saline. Right panel. Mean (+/- SEM) terminal (trials 13-14) number of infusions self-administered by rats housed in the enriched environment (EE) in the saccharin-saline (white bar), saccharin-cocaine low (light gray bar), or saccharin-cocaine high (dark gray bar) condition.

Figure 4

Left panel. Mean (+/- SEM) terminal (trials 13-14) latency (s) to self-administer the first infusion for rats housed in the non-enriched environment (Non-EE) in the saccharin-saline (white bar), saccharin-cocaine low (light gray bar), or saccharin-cocaine high (dark gray bar) condition. * denotes statistical significance (p < 0.01) compared to Non-EE saccharin-cocaine low and Non-EE saccharin-saline. Right panel. Mean (+/- SEM) terminal (trials 13-14) latency (s) to self-administer the first infusion for rats housed in the enriched environment (EE) in the saccharin-saline (white bar), saccharin-cocaine low (light gray bar), or saccharin-cocaine high (dark gray bar) condition. # denotes statistical significance (p < 0.03) compared to EE saccharin-cocaine-low and EE saccharin-saline.

Figure 5

Left panel. Mean (+/- SEM) number of infusions self-administered during the final progressive ratio (PR) test by rats housed in the non-enriched environment (Non-EE) in the saccharin-saline (white bar), saccharin-cocaine low (light gray bar), or saccharin-cocaine high (dark gray bar) condition. * denotes statistical significance (p < 0.01) compared to Non-EE saccharin-cocaine low and Non-EE saccharin-saline. Right panel. Mean (+/- SEM) number of infusions self-administered during the final PR test by rats housed in the enriched environment (EE) in the saccharin-saline (white bar), saccharin-cocaine low (light gray bar), or saccharin-cocaine high (dark gray bar) condition.

Figure 6

Mean (+/- SEM) saccharin intake (licks/5 min). a) Left panel. Mean (+/- SEM) saccharin intake (licks/5 min) across trials for rats housed in the non-enriched environment (Non-EE) in the saccharin-saline (white circles), saccharin-cocaine low (black circles), or saccharin-cocaine high (black triangles) condition. * denotes statistical significance (ps < 0.02) compared to Non-EE saccharin-cocaine low and # and & denote statistical significance (ps < 0.04 and ps < 0.03, respectively) compared to Non-EE saccharin-cocaine high. Right panel. Mean (+/- SEM) saccharin intake (licks/5 min) across trials for rats housed in the enriched environment (EE) in the saccharin-saline (white circles), saccharin-cocaine low (black circles), or saccharin-cocaine high (black circles) condition. * denotes statistical significance (ps < 0.03) compared to EE saccharin-cocaine low. b) Left panel. Mean (+/- SEM) terminal (trials 13-14) saccharin intake (licks/5 min) for rats housed in the non-enriched environment (Non-EE) in the saccharin-saline (white bar), saccharin-cocaine low (light gray bar), or saccharin-cocaine high (dark gray bar) condition. * denotes statistical significance (p < 0.01) compared to Non-EE saccharin-cocaine low and Non-EE saccharin-cocaine high and # denotes statistical significance (p = 0.05) compared to Non-EE saccharin-cocaine high. Right panel. Mean (+/- SEM) terminal (trials 13-14) saccharin intake (licks/5 min) for rats housed in the enriched environment (EE) in the saccharin-saline (white bar), saccharin-cocaine low (light gray bar), or saccharin-cocaine high (dark gray bar) condition. & denotes statistical significance (p < 0.03) compared to EE saccharin-cocaine low and EE saccharin-cocaine high.