Disrupted social development enhances the motivation for cocaine in rats

Abstract

Rationale: Early social experiences are of major importance for behavioural development. In particular, social play behaviour during post-weaning development is thought to facilitate the attainment of social, emotional and cognitive capacities. Conversely, social insults during development can cause long-lasting behavioural impairments and increase the vulnerability for psychiatric disorders, such as drug addiction.

Objectives: The aim of this study was to investigate whether a lack of social experiences during the juvenile and early adolescent stage, when social play behaviour is highly abundant, alters cocaine self-administration in rats.

Methods: Rats were socially isolated from postnatal days 21 to 42 followed by re-socialization until adulthood. Cocaine self-administration was then assessed under a fixed ratio and progressive ratio schedule of reinforcement. Next, cue, cocaine and stress-induced reinstatement of cocaine seeking was determined following extinction of self-administration.

Results: Early social isolation resulted in an enhanced acquisition of self-administration of a low dose (0.083 mg/infusion) of cocaine, but the sensitivity to cocaine reinforcement, assessed using a dose-response analysis, was not altered in isolated rats. Moreover, isolated rats displayed an increased motivation for cocaine under a progressive ratio schedule of reinforcement. Extinction and reinstatement of cocaine seeking was not affected by early social isolation.

Conclusions: Early social isolation causes a long-lasting increase in the motivation to self-administer cocaine. Thus, aberrations in post-weaning social development, such as the absence of social play, enhance the vulnerability for drug addiction later in life.

Figure 1

Effects of social isolation during PND 21–42 followed by re-socialization on acquisition of intravenous cocaine self-administration at 0.083 mg/infusion (session 1–5) and 0.25 mg/infusion (session 6–10) in adulthood. (A) The number of rewards (2 hr) and (B) intake of cocaine (mg/2 hr) during the first 10 cocaine self-administration sessions. (C) Number of rewards during the 5^th session and (D) 10^th session expressed in 20 min bins. SOC=socially reared rats during PND 21–42 (n=13), ISO=socially isolated rats during PND 21–42 (n=14). Data represents mean+SEM. * p<0.05 compared to SOC

Figure 2

Effects of social isolation during PND 21–42 followed by re-socialization on within-session dose response curve of cocaine self-administration in adulthood. Graphs illustrate (A) the number of cocaine infusions (rewards) and (B) cocaine intake (mg/hr). SOC=socially reared rats during PND 21–42 (n=12), ISO=socially isolated rats during PND 21–42 (n=12). Data represents mean+SEM.

Figure 3

Effects of social isolation during PND 21–42 followed by re-socialization on breakpoints under a PR schedule of reinforcement at (A) 0.083 mg/infusion of cocaine or (B) 0.25 mg/infusion of cocaine in adulthood. SOC=socially reared rats during PND 21–42 (0.083 mg/infusion: n=12; 0.25 mg/infusion: n=11), ISO=socially isolated rats during PND 21–42 (0.083 mg/infusion: n=13; 0.25 mg/infusion: n=11). Data represents mean+SEM. * p<0.05 compared to SOC

Figure 4

Effects of social isolation during PND 21–42 followed by re-socialization on (A) cue-induced cocaine seeking, (B) extinction of cocaine self-administration, (C) cocaine- and (D) yohimbine-induced reinstatement of cocaine seeking in adulthood. SOC=socially reared rats during PND 21–42 (n=11), ISO=socially isolated rats during PND 21–42 (n=11). Data represents mean+SEM. $ p<0.05 compared to day 1, # indicates p<0.05 compared to 0 mg/kg.