NMDA receptor complex antagonists have potential anxiolytic effects as measured with separation-induced ultrasonic vocalizations

Parental Deprivation Induces N‐Methyl‐D‐Aspartate‐Receptor Upregulation in Limbic Brain Areas of Octodon degus: Protective Role of the Maternal Call

“…A participation of NMDA receptor activation in emotional stress during parental separation has been shown in pharmacological behavioral experiments in pups of laboratory rats, in which the application of NMDA receptor antagonists suppressed ultrasonic vocalizations which represent a reliable indicator for fear and anxiety (Kehne et al, 1991 (Shors & Mathew, 1998;McEwen, 1999) by stimulating pituitary hormone release Zelena et al, 1999) and the synthesis and release of dopamine within the striatum, hippocampus, substantia nigra (Doherty & Gratton, 1997;Zigmond et al, 1998), ventral tegmental area, and PFC (Jedema & Moghaddam, 1994;Takahata & Moghaddam, 1998). An increase of AMPA but not ofNMDA receptors has been found after 1 h of acute immobilization/shock stress (Tocco et al, 1991); after repeated immobilization stress, levels of GIuR1 mRNA were elevated in the hippocampus (Schwendt & Jezova, 2000), whereas social stress induced a decrease of AMPA receptors (Krugers et al, 1993).…”

“…Quite analogous to the impaired functional maturation of the sensory systems after sensory deprivation, either early socio-emotional deprivation or adverse, stressful emotional experiences may induce an impaired or altered development of the limbic pathways. Such functional deficits in the limbic system may be the neural correlate of behavioral disturbances and cognitive and emotional deficits, which are typically observed in socially deprived animals and humans (Hall, 1998;Suomi, 1991;Spitz, 1945; Skeels, 1966 Poeggel et al, 1999;Thoa et al, 1976;Weinstock et al, 1978;Jones et al, 1992), but only a few studies analyzing changes on the receptor level have been performed (Liu et al, 2000 (Lil-Jequist et al, 1993) and are activated by stressful events (Shors & Mathew, 1998), including the expression of anxiety that is induced by maternal separation (Kehne et al, 1991). NMDA receptors participate in processes of juvenile and adult learning (Hattori et al, 1990;Flood & Morley, 1998, Bock et al, 1996Roullet et al., 1999), brain maturation (Hattori & Wasterlain, 1990), neuronal plasticity (Staubli, 1995;Bock & Braun, 1999), and formation of spatial memory (lzquierdo & Medina, 1997;Guitierrez et al, 1999).…”

Reduced isolation-induced aggressiveness in mice following NAALADase inhibition

“…Chronic administration of classic antidepressants, as well as serotonin reuptake inhibitors, alters radioligand binding to NMDA receptors, and reduces the expression of mRNA encoding NMDA receptor subunits in cortex, striatum, and amygdala (Skolnick et al 1996;Nowak et al 1998;Skoknick 1999). Similarly to classic antidepressants, chronic administration of NMDA antagonists decreases b-receptors (reviewed in Berman 2000; Petrie et al 2000), and reduces behavioral deficits in animal models of anxiety (Winslow et al 1990; Kehne et al 1991;Blanchard et al 1992;Xie and Commissaris 1992;Wiley et al 1995;Przegalinski et al 1996;Belzung and Berton 1997;Wiley 1997) and depression .…”

MDL 26,479: a potential cognition enhancer with benzodiazepine inverse agonist‐like properties

“…SIV have been used by a number of investigators to assess potential anxiolytic activity of compounds (Gardner, 1985;Mos et al, 1988;Insel et al, 1988;Kehne et al, 1991). Also, anxiolytic benzodiazepines suppress SIV (Gardner, 1985;Insel et al, 1986) whereas anxiogenic agents such as the GABA antagonist, PTZ, or P-carboline inverse agonists inc- rease SIV.…”

“…Ultrasonic vocalizations were measured as previously described (Kehne et al, 1991 (Kehne & Davis, 1985;Kehne et al, 1992). Briefly, a stabilimeter equipped with a movement-sensitive transducer measured the amplitude of a startle reflex elicited by an acoustic stimulus (50 ms, 120 dB while noise burst) or by a tactile stimulus (50 ms, 4 PSI air puff, delivered to the rat's back).…”