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Rats exhibit ‘empathy’ making them a model to understand the neural underpinnings of such behavior. We show data consistent with these findings, but also that behavior and dopamine (DA) release reflects subjective rather than objective evaluation of appetitive and aversive events that occur to another. We recorded DA release in two paradigms: one that involved cues predictive of unavoidable shock to the conspecific and another that allowed the rat to refrain from reward when there were harmful consequences to the conspecific. Behavior and DA reflected pro-social interactions in that DA suppression was reduced during cues that predicted shock in the presence of the conspecific and that DA release observed on self-avoidance trials was present when the conspecific was spared. However, DA also increased when the conspecific was shocked instead of the recording rat and DA release during conspecific avoidance trials was lower than when the rat avoided shock for itself. 

We report investigations of the use of cucurbit[8]uril (CB[8]) macrocycles as an antidote to counteract the in vivo biological effects of phencyclidine. We investigate the binding of CB[8] and its derivative Me₄CB[8] toward ten drugs of abuse (3–9,12–14) by a combination of¹H NMR spectroscopy and isothermal titration calorimetry in phosphate buffered water. We find that the cavity of CB[8] and Me₄CB[8] are able to encapsulate the 1‐amino‐1‐aryl‐cyclohexane ring system of phencyclidine (PCP) and ketamine as well as the morphinan skeleton of morphine and hydromorphone withK_dvalues ≤50 nm. In vitro cytotoxicity (MTS metabolic and adenylate kinase cell death assays in HEK293 and HEPG2 cells) and in vivo maximum tolerated dose studies (Swiss Webster mice) which were performed for Me₄CB[8] indicated good tolerability. The tightest host⋅guest pair (Me₄CB[8]⋅PCP;K_d=2 nm) was advanced to in vivo efficacy studies. The results of open field tests demonstrate that pretreatment of mice with Me₄CB[8] prevents subsequent hyperlocomotion induction by PCP and also that treatment of animals previously dosed with PCP with Me₄CB[8] significantly reduces the locomotion levels.