cinanserin and 1-(3-trifluoromethylphenyl)piperazine

Simultaneous single-unit and intracortical activity were recorded from neocortical neurons in urethane-anaesthetized rats to investigate the role of serotonin (5-HT) in modifying cortical excitability. Units, at a depth of 775-1100 microns from the pial surface, discharged in a burst-pause pattern that was correlated with slow wave activity. Application of noxious somatic stimulation resulted in cortical desynchronization and altered the pattern of unit activity such that firing was continuous, i.e., the pauses were eliminated. Intravenous administration of the mixed 5-HT1C/5-HT2 antagonists (cinanserin, cyproheptadine, ketanserin, and ritanserin) prevented both desynchronization and the change in unit activity induced by noxious stimulation within 2.5-15 min of the injection. The basic pattern of burst-pause activity remained intact, but the number of spikes per burst was typically reduced, whereas interburst intervals were increased. Iontophoretic application of these antagonists onto cortical neurons resulted in actions similar to those observed following systemic administration. Intravenous and iontophoretic application of m-trifluomethylphenylpiperazine (5-HT1C agonist, 5-HT2 antagonist) resulted in actions indistinguishable from those observed with the above antagonists, from which we conclude 5-HT2 and not 5-HT1C receptors mediate the alteration in unit activity observed with noxious stimulation. The results are discussed with respect to an interaction between N-methyl-D-aspartate and 5-HT2 receptors leading to the enhanced unit activity observed with noxious stimulation.

Topics: Animals; Cerebral Cortex; Cinanserin; Cyproheptadine; Iontophoresis; Ketanserin; Male; Microelectrodes; Neurons; Pain; Physical Stimulation; Piperazines; Rats; Rats, Sprague-Dawley; Receptors, Serotonin; Ritanserin; Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists

The behavioral effects of the serotonin (5-HT) precursor l-5-hydroxytryptophan (l-5-HTP) and the phenylpiperazine 5-HT agonists 6-chloro-2-(1-piperazinyl)pyrazine (MK-212), 1-(m-trifluromethylphenyl) piperazine (TFMPP), 1-(m-chlorophenyl)piperazine (CPP) and 2-(1-piperazinyl)quinoline (quipazine) were compared with those of the putative 5-HT antagonists metergoline, methysergide, cyproheptadine, cinanserin and ketanserin under a multiple 5-min fixed-interval schedule of food or electric shock presentation in squirrel monkeys. Intramuscular administration of l-5-HTP (0.3-17 mg/kg), MK-212 (0.01-1.0 mg/kg), TFMPP and CPP (0.03-10 mg/kg) produced dose-related decreases in responding under both the food- and shock-presentation schedules. Quipazine differed from the other 5-HT agonists in that it increased shock-maintained behavior at doses (0.1-1.0 mg/kg) that decreased responding maintained by food. The 5-HT antagonists produced mixed behavioral effects. Metergoline (0.03-1.0 mg/kg), cyproheptadine (0.1-1.0 mg/kg) and cinanserin (1.0-10 mg/kg) produced dose-related increases in responding maintained by food, whereas only metergoline and methysergide increased behavior maintained by shock presentation. The prototype 5-HT2-receptor ligand ketanserin (0.3-10 mg/kg) differed from the other 5-HT antagonists in that it decreased behavior maintained by either event. Thus, performances maintained by food or shock presentation reveal both qualitative and quantitative differences in the behavioral effects of 5-HT receptor agonists and antagonists.

Topics: 5-Hydroxytryptophan; Animals; Cinanserin; Conditioning, Operant; Cyproheptadine; Electroshock; Female; Ketanserin; Male; Metergoline; Methysergide; Piperazines; Piperidines; Pyrazines; Quipazine; Receptors, Serotonin; Saimiri