213 97 97 4 4 François Jenck Chris L. E. Broekkamp Anton M. L. Van Delft C.N.S. Pharmacology Department Organon International B.V. P.O. Box 20 NL-5340 BH Oss The Netherlands Abstract The effects of serotonin receptor antagonists with differential selectivity for the various classes of 5HT receptors (5HT 1 , 5HT 2 and 5HT 3 ) were tested for their effects on the response to aversive brain stimulation. Electrical stimulation was administered to the dorsal part of the periaqueductal gray matter (PAG), one of the main cerebral structures subserving negative reinforcement. Stimulation frequency thresholds for escape responses were recorded before and following administration of the compounds. Ketanserin (0.32–32 mg/kg IP), trazodone (1.0–22 mg/kg), pirenperone (0.032–1.0 mg/kg) and spiperone (0.1–0.2 mg/kg) dose-dependently increased stimulation frequency thresholds necessary to induce escape responses. Opposite effects were observed with mianserin (0.01–32 mg/kg) and metergoline (0.032–10 mg/kg) which decreased threshold for escape. ICS 205-930 (0.01–10 mg/kg), MDL 72222 (0.1 22 mg/kg) and GR 38032 F (0.1–10 mg/kg) did not affect the stimulation frequency threshold for escape. Prazosin (0.1–2.2 mg/kg) did not specifically affect aversive brain stimulation. Haloperidol (0.02–1.0 mg/kg) increased the frequency threshold for escape responses but with some motoric side effects. These data show that the various types of 5HT receptors differentially contribute to the control of central aversive systems in rats. It is suggested that blockade of 5HT 2 receptors suppresses the central aversive system, whereas blockade of some 5HT 1 receptors enhances aversion and overcomes the 5HT 2 -mediated suppression. Blockade of 5HT 3 receptors has no effects. Dopamine receptor blockade further contributes to the suppression of the central aversive system. The relevance of these findings to some pathophysiological mechanisms of anxiety and depressive disorders is discussed.
Psychopharmacology – Springer Journals
Published: Apr 1, 1989
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