tropisetron and 4-iodo-2-5-dimethoxyphenylisopropylamine

Serotonin (5-HT) receptor interaction in the control of female rat lordosis behavior was examined. Ovariectomized rats, with bilateral implants in the ventromedial nucleus of the hypothalamus (VMN), were hormonally primed with 25 micrograms estradiol benzoate and 500 micrograms progesterone. Rats were infused with the 5-HT3 receptor antagonist, 3-tropanyl-indole-3 carbonylate (tropisetron; 500 ng), or were coinfused with the 5-HT3 receptor antagonist and the 5-HT2A/2C receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI; 500, 1500, or 2000 ng). Additional ovariectomized, hormone-primed rats received bilateral VMN infusions with the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT; 200 ng), or were coinfused with the 5-HT1A receptor agonist and the 5-HT3 receptor agonist, m-chlorophenyl-biguanide (mCPBG; 250, 500, or 1000 ng). Lordosis behavior was observed prior to VMN infusion, during the infusion and for 30 consecutive minutes thereafter. Tropisetron reduced the lordosis to mount (L/M) ratio in every animal investigated but the decline was attenuated by coinfusion with DOI. Similarly, the L/M ratio declined following infusion with 8-OH-DPAT and the decline was dose-dependently reduced by coinfusion with mCPBG. Only the 5-HT3 receptor agonist altered the quality of the lordosis reflex. These studies provide evidence that the effects of 5-HT on female rat lordosis behavior involve the integrated activity of at least 3 different 5-HT receptor families.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Amphetamines; Animals; Biguanides; Drug Combinations; Female; Indoles; Ovariectomy; Rats; Rats, Inbred Strains; Receptors, Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists; Sexual Behavior, Animal; Tropisetron

Previously, we have shown that serotonin (5-HT) can inhibit, excite, or biphasically inhibit and excite individual neurons of the ventromedial nucleus (VMN) in hypothalamic slices from female rats. In the present study, similar in vitro methods were used to further characterize VMN neurons responsive to 5-HT, and to identify the receptor subtypes involved in mediating these 5-HT actions. Results from a dose-response experiment indicate that increasing the dose of 5-HT can transform an inhibitory response into a biphasic or even an excitatory response. This indicates that modulation of 5-HT release in the VMN could alter the net response of the VMN to this transmitter. By comparing the actions of 5-HT with the effects of selective agonists and antagonists, the inhibitory action was found to be mediated predominantly, if not exclusively, by 5-HT1A receptors, while the excitatory action was mediated predominantly or exclusively through 5-HT2 receptors. There appear to be few, if any, 5-HT3 receptors in the VMN, and their functions are unclear. The inhibitory and the excitatory phases of the biphasic responses were not mediated together by a single receptor subtype but were mediated separately by 5-HT1A and 5-HT2 receptors, respectively. The presence of the biphasic response in a large proportion of neurons, therefore, indicates the coexistence of different subtypes of 5-HT receptors in many individual VMN neurons. The use of selective agonists and antagonists further indicates that the coexistence also occurs in neurons showing monophasic responses, and that the opposite actions mediated by the coexisting receptor subtypes can interact with each other. Therefore, changing the ratio of coexisting receptor subtypes could modify the net output of the VMN response to 5-HT. Together with behavioral studies by others, it emerges from our findings that the inhibitory action of 5-HT on VMN neurons is associated with, and may be responsible for, the stimulation of feeding and inhibition of lordosis, while the excitatory action is related and may lead to the opposite behavioral effects. Finally, with the coexistence in VMN neurons of two receptor subtypes that can mediate 5-HT effects on both feeding and lordosis, the VMN can serve as a substrate for 5-HT to coordinate these two behaviors.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Amphetamines; Animals; Electrophysiology; Feeding Behavior; Female; In Vitro Techniques; Indoles; Neural Inhibition; Neurons; Piperazines; Rats; Rats, Sprague-Dawley; Receptors, Serotonin; Serotonin; Serotonin Antagonists; Sexual Behavior, Animal; Tropisetron; Ventromedial Hypothalamic Nucleus

Cocaine inhibits the 5-HT2-mediated (+/-)-DOI-induced head-twitch response (HTR) in mice in a dose-dependent manner. In order to investigate the possible inhibitory mechanism(s) of cocaine on 5-HT2 receptor function, we studied the effects of the selective adrenergic alpha 2 receptor antagonist yohimbine and the beta-adrenergic/5-HT1 receptor antagonist alprenolol, and the 5-HT3 antagonist ICS 205-930 on the inhibitory action of cocaine on the (+/-)-DOI-induced HTR. Neither yohimbine (0.1 and 0.5 mg/kg) nor alprenolol (10 mg/kg) pretreatment had any significant effect on the (+/-)-DOI-induced HTR. However, both antagonists prevented the inhibitory effects of cocaine on the (+/-)-DOI-induced HTR. The 5-HT3 antagonist ICS 205-930 neither produced HTR nor decreased the (+/-)-DOI-induced HTR frequency. The present results suggest that cocaine inhibits 5-HT2 receptor function by increasing the synaptic concentration of norepinephrine and serotonin via inhibition of their uptake and thus indirectly stimulating the respective inhibitory adrenergic alpha 2 and serotonergic 5-HT1A receptors. Furthermore, cocaine's 5-HT3 antagonist properties appear not to play a role in the inhibition of head-twitch behavior.

Topics: Adrenergic alpha-Agonists; Alprenolol; Amphetamines; Animals; Brain Chemistry; Cocaine; Dose-Response Relationship, Drug; Indoles; Male; Mice; Mice, Inbred ICR; Norepinephrine; Receptors, Serotonin; Serotonin; Serotonin Antagonists; Stimulation, Chemical; Tropisetron; Yohimbine