ABSTRACT
Most of the pharmacological actions of ketamine, in both clinical and illicit use, are attributed to actions that are mediated by the central nervous system (CNS). The neurotransmitter dopamine is implicated in disorders such as Parkinson’s disease and psychosis. Phencyclidine, which is also an NMDA receptor antagonist much like ketamine, also binds to the ion channel site of NMDA receptors and possesses dopamine-like properties as well. For example, prolactin secretion is suppressed and rotational behavior is increased by phencyclidine in rodents (Lozovsky et al. 1983; Mele et al. 1998). The increased locomotor activity observed in rats is blocked more effectively by the D1 receptor antagonist SCH23390 than the D2 receptor antagonist raclopride in the nucleus accumbens (NAc) (Matulewicz et al. 2010). Ketamine also increases the association (or binding potential) of D1 receptors in the rat striatum (Momosaki et al. 2004). The availability of D1 receptors is higher in ketamine users in the human prefrontal cortex (Narendran et al. 2005). The binding potential of D1 receptors in these human subjects positively correlated with the extent of ketamine use (Narendran et al. 2005). The interactions of ketamine with dopamine receptors may underlie dopamine-associated prefrontal impairments, notably working memory decits that are often seen in chronic ketamine users (Brozoski et al. 1979). Monkeys treated with ketamine demonstrate cognitive and behavioral symptoms that resemble those of schizophrenia (Roberts et al. 2010). The atypical antipsychotic risperidone, which blocks D2 receptors, did not alleviate ketamine-induced symptoms (Roberts et al. 2010). Instead, prior activation of D1 receptors (by the full agonist A77646 or by the partial agonist SKF38393) improves spatial memory performance (Roberts et al. 2010). Gross motor and hallucinatorylike behaviors are reduced by SKF38393 but not by A77646, a nding the authors attributed to the more specic D1 receptor-mediated actions on working memory (Roberts et al. 2010). The function of D1 receptors in the
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