Figure 6.

(A) Relationship between elevation in ICSS reward thresholds and cocaine intake escalation (Left). Percent change from baseline response latencies (3 h and 17–22 h after each self-administration session; first data point indicates 1 h before the first session) (Right). Percent change from baseline ICSS thresholds. *p < 0.05, compared with drug-naive and/or ShA rats (tests for simple main effects) [taken with permission from Ref. (97)]. (B) Unlimited daily access to heroin escalated heroin intake and decreased the excitability of brain reward systems (Left). Heroin intake (±SEM; 20 μg per infusion) in rats during limited (1 h) or unlimited (23 h) self-administration sessions. ***p < 0.001, main effect of access (1 or 23 h) (Right). Percent change from baseline ICSS thresholds (±SEM) in 23 h rats. Reward thresholds, assessed immediately after each daily 23 h self-administration session, became progressively more elevated as exposure to self-administered heroin increased across sessions. *p < 0.05, main effect of heroin on reward thresholds [taken with permission from Ref. (99)]. (C) Escalation in methamphetamine self-administration and ICSS in rats. Rats were daily allowed to receive ICSS in the lateral hypothalamus 1 h before and 3 h after intravenous methamphetamine self-administration with either 1 or 6 h access (Left). Methamphetamine self-administration during the first hour of each session (Right). ICSS measured 1 h before and 3 h after methamphetamine self-administration. *p < 0.05, **p < 0.01, ***p < 0.001, compared with session 1. ^#p < 0.05, compared with LgA 3 h after [taken with permission from Ref. (98)].