Effects of strain and serotonergic agents on prepulse inhibition and habituation in mice

Sensorimotor gating is critical to normal brain functioning, and disruptions are associated with certain mental illnesses, such as schizophrenia. Prepulse inhibition of the acoustic startle reflex (ASR) (PPI) is an operational measure of sensorimotor gating, of which evidence for a serotonergic modulation is currently inconsistent. In a double-blind placebo-controlled crossover design, 18 healthy male volunteers received either placebo or a dose of 10 mg of escitalopram (SSRI), after which they were tested in both PPI and habituation of the startle reflex paradigms. No significant differences between the two treatments were observed on PPI, although escitalopram was found to significantly delay habituation of the ASR. In the current study, escitalopram was found to delay habituation, but it did not affect PPI in healthy male volunteers. As escitalopram is a highly specific SSRI, the results suggest that an increased serotonergic activity disrupts habituation, but not PPI in healthy volunteers.

Section: Discussionmentioning

confidence: 94%

The Effects of Increased Central Serotonergic Activity on Prepulse Inhibition and Habituation of the Human Startle Response

Jensen

Oranje

Wienberg

et al. 2007

“…PPI was included as a control for normal sensory motor gating (SMG). SMG is a neural mechanism that allows the generation of appropriate behavioral responses to incoming sensory cues and the inhibition of extraneous sensory, cognitive, and motor information (Dulawa and Geyer, 2000). Normal sensory motor functioning is critical to many of the behavioral tasks in these experiments.…”

Section: Discussionmentioning

confidence: 99%

“…Startle and sensorimotor gating was assessed using acoustic startle and PPI using a modified version of that used by Dulawa and Geyer (2000). For acoustic startle, mice were exposed to pulses of 90, 100, 110, and 120 dB in a pseudorandomized order with 20 presentations of each stimulus and an ITI of 30 s. For PPI, mice received multiple 40 ms 120 dB tones (startle alone) intermittently proceeded by four different prepulse signals (from 6 to 14 dB above background).…”

Section: Open Fieldmentioning

confidence: 99%

Profound Impairment in Social Recognition and Reduction in Anxiety-Like Behavior in Vasopressin V1a Receptor Knockout Mice

Bielsky

Szegda

et al. 2003

472

338

Considerable evidence suggests that arginine vasopressin (AVP) is critically involved in the regulation of many social and nonsocial behaviors, including emotionality. The existence of two AVP receptors in the brain, namely the V1a and V1b subtypes, and the lack of clear pharmacological data using selective agonists or antagonists, make it difficult to determine which receptor is responsible for the AVP-mediated effects on behavior. Here we report the behavioral effects of a null mutation in the V1a receptor (V1aR) in male mice. Male mice lacking functional V1aR (V1aRKO) exhibit markedly reduced anxiety-like behavior and a profound impairment in social recognition. V1aRKO performed normally on spatial and nonsocial olfactory learning and memory tasks. Acute central administration of AVP robustly stimulated stereotypical scratching and autogrooming in wild-type (WT), but not V1aRKO males. AVP and oxytocin (OT) mRNA and OT receptor-binding levels were similar in WT and V1aRKO mice. Given the current findings, the V1aR may provide a novel potential pharmacological target for social and affective disorders including autism, and anxiety disorders.

“…Conceivably, these effects might be somewhat different from those in rats, given the substantial differences in startle and PPI indices that have been documented based on strain and species background (Ralph and Caine, 2005;Swerdlow et al, 2005). Serotonergic agents in mice exhibit strain differences in PPI, habituation, and startle reactivity (Dulawa and Geyer, 2000). The serotonin releaser methylene-dioxy-methamphetamine disrupts PPI in rats, but increases PPI in humans (Vollenweider et al, 1999;Liechti et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Norepinephrine Transporter Blockade can Normalize the Prepulse Inhibition Deficits Found in Dopamine Transporter Knockout Mice

Yamashita

Fukushima

Shen

et al. 2006

Dopamine transporter knockout (DAT KO) mice display deficits in sensorimotor gating that are manifested by reduced prepulse inhibition (PPI) of the acoustic startle reflex. Since PPI deficits may model some of the cognitive dysfunctions identified in certain neuropsychiatric patients, we have studied the effects of transporter blockers on PPI in wild-type and DAT KO mice. Treatments with High dose psychostimulants that block DAT as well as the norepinephrine (NET) and serotonin (SERT) transporters (60 mg/kg cocaine or methylphenidate) significantly impaired PPI in wild-type mice. By contrast, these treatments significantly ameliorated the PPI deficits observed in untreated DAT KO mice. In studies with more selective transport inhibitors, the selective NET inhibitor nisoxetine (10 or 30 mg/kg) also significantly reversed PPI deficits in DAT KO mice. By contrast, while the SERT inhibitor fluoxetine (30 mg/kg) normalized these PPI deficits in DAT KO mice, citalopram (30 or 100 mg/kg) failed to do so. The 'paradoxical' effects of cocaine and methylphenidate in DAT KO mice are thus likely to be mediated, at least in part by the ability of these drugs to block NET, although serotonin systems may also have some role. Together with recent microdialysis data, these results support the hypothesis that prefrontal cortical NET blockade and consequent enhancement of prefrontal cortical extracellular dopamine mediates the reversal of PPI deficits in DAT KO mice.