40 Taken together, serotonergic hallucinogens and psychotomimetic NM..DA antagonists produce schizophrenia-like deficits in behavioral measures of sensory gating such as PPI, and do so by actions localized to different parts of the CSPT circuitry. Despite their different primary mechanisms and sites of action, however, a common denominator of the effects of these drug classes is that they alter the dynamics of the integrated Inhibitors,research,lifescience,medical CSPT circuitry such that normal information processing is

distorted by deficits in fundamental forms of sensorimotor gating. Serotonergic amphetamines; MDMA Psychological effects In contrast to serotonergic hallucinogens and NMDA antagonists, a typical recreational and nontoxic dose of MDMA (1.5-7 mg/kg PO) produces an affective state of enhanced mood, profound Inhibitors,research,lifescience,medical well-being, happiness, increased extroversion and sociability, slight derealization and depersonalization, little anxiety, and moderate thought disturbances, but no hallucinations in normal volunteers.95 Depersonalization phenomena are mild and, in contrast to hallucinogens (eg, psilocybin), not experienced as problematic or psychotic fusion, but experienced as a pleasurable state of loosened ego boundaries as measured by the APZ questionnaire (Figure 2). Similar findings were reported with MDMA

and its congener MDE in healthy Inhibitors,research,lifescience,medical volunteers.96-100 Brain imaging studies To identify the functional neuroanatomy involved in the action of MDMA in humans, the effect of MDMA (1.7 mg/kg) versus placebo on regional cerebral blood flow (C.BF) was investigated in MDMA-naive human subjects using PET and Inhibitors,research,lifescience,medical [H2 15O]-PET.101 M.DMA moderately increased brain activity as indexed by CBF bilaterally in the ventromedial prefrontal cortex, the ventral NVP-BGJ398 molecular weight anterior cingulate, the inferior temporal lobe, and the medial occipital cortex and in the cerebellum. Decreases in CBF were found bilaterally in the motor and somatosensory cortex, Inhibitors,research,lifescience,medical the superior temporal lobe, the dorsal cingulate cortex, the insula, and the

thalamus. Unilateral decreases were found in the left amygdala, and the right parahippocampus. This activation pattern and associated affective state, which was characterized by heightened mood, increased extroversion, slight derealization, Cediranib (AZD2171) and intensification of vision, substantially differ from those seen in ketamine- and psilocybin-induced psychosis-like syndromes. The activation of prefrontal and related limbic/paralimbic structures in conjunction with deactivation of the amygdala may underlie the emotional effects of MDMA. This view is consistent with findings implicating the amygdala,102,103 orbitofrontal cortex,103 ventral anterior cingulate cortex,103,104 prefrontal cortex, temporal lobe, and thalamus104 in the regulation of mood and emotion. In this network, the amygdala appears to play a pivotal role in the mediation of both positive and negative emotions.