The Serotonergic Agonists Quipazine, CGS-12066A, and α-Methylserotonin Alter Motor Activity and Induce Hindlimb Stepping in the Intact and Spinal Rat Fetus.

Abstract

The effects of serotonergic agonists were examined in intact and spinal fetuses, using an in vivo fetal rat preparation. On Gestational Day 20, fetuses were prepared with a midthoracic or sham spinal transection. Dose-response curves were obtained for quipazine (nonselective 5-hydroxytryptamine [5-HT] agonist; 1.0-10.0 mg/kg), CGS-12066A (5-HT-sub(1B) agonist; 1.0-30.0 mg/kg), and alpha-methylserotonin (alpha-Me-5-HT; 5-HT-sub-2 agonist; 0.2-15.0 mg/kg). During a 10-min test, each of the agonists (delivered via intraperitoneal injection) influenced fetal behavior: They increased the occurrence of head movements, mouthing, and hindlimb stepping. Quipazine and alpha-Me-5-HT also promoted hindlimb activity in spinal fetuses. Thus, stimulation of the fetal 5-HT system modulates motor activity at multiple levels of the developing central nervous system.

Biotransformation of 3-Amino-5,6,7,8-tetrahydro-2-{4-[4-(quinolin-2-yl)piperazin-1-yl]butyl}quinazolin-4(3H)-one (TZB-30878), a Novel 5-Hydroxytryptamine (5-HT)1A Agonist/5-HT3 Antagonist, in Human Hepatic Cytochrome P450 Enzymes

“…At the time of M6 formation, quipazine, a nonselective 5-HT agonist, was released. The pharmacological activity was much lower than that of TZB-30878 (Brumley and Robinson, 2005). One of the major metabolic pathways was caused by formation of the cyclic metabolite M6 via intermediates M7 and M8.…”

Maternal anesthesia via isoflurane or ether differentially affects pre‐and postnatal behavior in rat offspring

“…Essentially all pharmacological agents undergo transplacental drug transfer (Benitz & Druzin, 2005;Nau & Plonait, 1998), including general anesthetics that can induce varying degrees of fetal anesthesia and behavioral depression (Ostheimer, 1984). Ether is relatively inexpensive, readily available, and easy to administer, and therefore continues to be the most commonly used maternal anesthetic in psychobiological investigations of perinatal rats (Brumley & Robinson, 2005;Kleven, Lane, & Robinson, 2004;Kozlov, Petrov, Varlinskaya, & Spear, 2006;Petrov, Nizhnikov, Varlinskaya, & Spear, 2006;Robinson, 2005;Smotherman, 2002Smotherman, , 2003. Ether, however, is characterized by high blood solubility that can be associated with accumulation in the fetal blood and tissues, and altered neurobehavioral function (Hodgkinson, Marx, Kim, & Miclat, 1977;Palahniuk, Scatliff, Biehl, Wiebe, & Sankaran, 1977).…”

Effects of Assist-as-needed Robotic Training Paradigms on the Locomotor Recovery of Adult Spinal Mice

“…Since its primary production is in the raphe nucleus in the brain, post SCI the level of serotonin decrease drastically in the spinal cord caudal to the lesion. It has been previously observed that pharmacological treatment with the drug quipazine can facilitate stepping in animals whose spinal cords have been completely severed [5][6][7]. In addition, we have shown previously that the level of recovery is greater when robotic training is combine with the admini-stration of quipazine [8].…”

“…However, fixed, repetitive training is very likely to be suboptimal, as variability is an intrinsic property of mammalian locomotion [5]. Hence, fixed locomotor training may lead to the phenomena of "learned helplessness" [6,7]. That is, the lower spinal cord becomes habituated to the training trajectory.…”