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Intravenous administration of m-chloro-phenylpiperazine (mCPP) (0.25 or 2.5 mg/kg) induced a marked and doserelated increase in extracellular concentrations of serotonin in hippocampus (300-1,400% of baseline) as measured using in vivo microdialysis in awake male Wistar rats of the spontaneously hypertensive (SH) strain. Indicating that the effect of mCPP was caused by a reversal of the serotonin transporter, it was antagonized by pretreatment with the serotonin re-uptake inhibitor citalopram (10 mg/kg) but was unaffected by local administration of the sodium channel blocker tetrodotoxin (TTX; 1 m). mCPP was also shown to induce an increase in extracellular concentrations of dopamine in the nucleus accumbens and the striatum of SH rats and in the nucleus accumbens of rats of the Sprague-Dawley (SD) Dopamine, In vivo microdialysis; Hippocampus; Striatum, Nucleus accumbens; Citalopram; Rat m-Chloro-phenylpiperazine (mCPP), the metabolite of the antidepressant drug trazodone, has recently gained marked attention as a putative probe of serotonergic function in clinical psychiatric research. Thus, the prolactin, ACTH, and cortisol responses to mCPP frequently have been used as putative markers of postsynaptic serotonin receptor function in various psychiatric disorders. Moreover, administration of mCPP has been shown to elicit, and/or aggravate, anxiety attacks in patients with panic disorder, obsessions in patients with obsessive compulsive disorder (OCD), elation in alcoholics and cocaine addicts, and positive symptoms in schizophrenic patients (see Murphy et al. 1991;Kahn and Wetzler 1991;Krystal et al. 1993;Buydens-Branchey et al. 1993;Krystal et al. 1994).mCPP displays high affinity to 5-HT2C receptors and moderate, or low, affinity to 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, and 5-HT3 receptors; in addition, the compound has some affinity for alpha-2-adrenoceptors. At the 5-HT2C receptor, mCPP seems to act as a partial agonist with relatively high intrinsic efficacy, whereas, at the other serotonin receptors, the intrinsic efficacy of mCPP is moderate or low (see Murphy et al. 1991 NO . 3 and Wetzler 1991). The behavioral and endocrine effects of mCPP observed in clinical studies are generally attributed to the direct effects of mCPP on various subtypes of serotonin receptors; in contrast, little attention has been paid to the report by Baumann et al. (1993) suggesting that mCPP may also stimulate serotonin release by means of an interaction with the serotonin transporter (see also Baumann et al. 1995).To further elucidate the possible influence of mCPP on the release of serotonin, we studied the effects of a high dose of mCPP on extracellular, hippocampal concentrations of serotonin in awake, freely moving rats using in vivo microdialysis.Enhanced dopaminergic neurotransmission has been suggested as a mechanism of importance both for the positive symptoms of schizophrenia and for the euphoria induced by such central stimulants as cocaine. The observations that mCPP may aggravate psychotic symptoms in schizophr...

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1. The amygdaloid complex is a key structure in mechanisms of fear and anxiety. Expression of the immediate-early gene c-fos has been reported in the central nucleus of the amygdala following various stressors, but the functional role of this phenomenon has remained unknown. 2. c-fos expression was observed in the central nucleus when rats were subjected to a pharmacologically validated animal model of anxiety, the Vogel conflict test, but not after mere exposure to the test apparatus. Bilateral amygdala injection of a 15-mer phosphorothioate c-fos antisense oligodeoxynucleotide prior to testing blocked conflict-induced c-fos expression and had behavioral effects similar to those of established antianxiety drugs. 3. Separate experiments determined that antisense treatment did not affect conflict behavior by acting on shock thresholds or drinking motivation. 4. These findings provide evidence that neuronal activation and c-fos induction in the amygdala may be of importance for mechanisms of fear and anxiety.