A novel rat strain with enhanced sensitivity to the effects of dopamine agonists on startle gating

Swerdlow, Neal R.; Breier, Michelle R.; Mora, Adrienne B.; Ko, David; Shoemaker, Jody M.

doi:10.1016/j.pbb.2007.08.013

Cited by 22 publications

(22 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this respect, oxytocin has similar effects as the atypical antipsychotics clozapine and quetiapine (Swerdlow et al, 2008) as well as the putative antipsychotic PD149163, which have also been shown to increase PPI in BN rats (Feifel et al, 2011). These data further add to the preclinical evidence supporting the notion that oxytocin has facilitatory effects on sensorimotor gating circuits in the brain and that it also has therapeutic potential in schizophrenia and perhaps other disorders.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The effects of oxytocin and its analog, carbetocin, on genetic deficits in sensorimotor gating

Feifel

Shilling

Belcher

2012

European Neuropsychopharmacology

View full text Add to dashboard Cite

Converging evidence from preclinical and clinical studies suggest that oxytocin has therapeutic potential for schizophrenia and other neuropsychiatric disorders. Prepulse inhibition of the startle reflex (PPI) is a measure of sensorimotor gating, an important brain function involved in filtering environmental information. We previously demonstrated that systemically administered oxytocin reversed psychostimulant-induced PPI deficits in rats suggesting that oxytocin can produce antipsychotic-like central effects. That finding was supported by a recent trial in humans, which found that intranasal oxytocin reduced symptoms of schizophrenia. The goal of this study was to extend this line of investigation by testing the effects of oxytocin, and a structural analog of oxytocin, carbetocin, on nonpharmacological deficits in PPI. In experiment 1, Brown Norway (BN) rats, a rat strain that has naturally low PPI, were given either saline or one of three doses of oxytocin (0.04 - 1.0 mg/kg, sc). In experiment 2, BN rats were given either saline, one of three doses of carbetocin (0.04 - 1.0 mg/kg) or oxytocin (1 mg/kg). PPI and acoustic startle response (ASR) of rats were tested. Oxytocin significantly increased PPI (P < 0.01) and decreased ASR levels (P < 0.01) in BN rats in a dose-dependent fashion. In contrast, carbetocin had no effect on PPI levels or ASR. The facilitation of BN PPI by oxytocin is similar to what we have previously observed with clozapine and thus further supports oxytocin having antipsychotic properties. In contrast to oxytocin, our data do not support the use of carbetocin as an antipsychotic drug.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Brown Norway (BN) rats have reduced PPI under certain parametric conditions and it has been suggested that these animals represent an appropriate model of schizophrenia, since they exhibit behavioral characteristics frequently reported in schizophrenia patients (Palmer et al, 2000; Swerdlow et al, 2008). …”

Section: Introductionmentioning

confidence: 99%

The effects of oxytocin and its analog, carbetocin, on genetic deficits in sensorimotor gating

Feifel

Shilling

Belcher

2012

European Neuropsychopharmacology

View full text Add to dashboard Cite

show abstract

“…One to two rats of each sex/litter/prenatal treatment of SS F1 offspring were mated with naïve B rats (Charles River, Wilmington, MA, USA) to generate SB and BS F2 progeny. B is the most phylogenetically divergent inbred rat strain (Swerdlow et al, 2008), and the B and S genomes have been sequenced by the Rat Genome Project and Celera, respectively. All of which increased the chances that we would be able to identify a single nucleotide polymorphism (SNP) between the B and S cDNAs at the Igf2 locus that we could use to measure allele-specific contribution to the expression of hippocampal Igf2 .…”

Section: Methodsmentioning

confidence: 99%

Intergenerational and parent of origin effects of maternal calorie restriction on Igf2 expression in the adult rat hippocampus

Harper

Tunc-Ozcan

Graf

et al. 2014

Psychoneuroendocrinology

View full text Add to dashboard Cite

Insulin-like growth factor 2 (Igf2) regulates development, memory and adult neurogenesis in the hippocampus. Calorie restriction (CR) is known to modulate non-neuronal Igf2 expression intergenerationally, but its effect has not been evaluated on brain Igf2. Here, Sprague-Dawley (S) dams underwent moderate CR between gestational days 8–21. To identify parent of origin expression pattern of the imprinted Igf2 gene, their offspring (SS F1) were mated with naïve male or female Brown Norway (B) rats to obtain the second generation (BS and SB F2) progeny. CR did not affect adult hippocampal Igf2 transcript levels in SS F1 males or their BS F2 progeny, but increased it in SS F1 females and their SB F2 offspring. The preferentially maternal Igf2 expression in the SB F2 control male hippocampus relaxed to biallelic with CR, with no effect of grandmaternal diet in any other groups. Thus, allele-specific and total expression of hippocampal Igf2 is affected by maternal, grandmaternal CR in a strain and sex-specific manner.

show abstract

“…Based on known significant sex differences in PPI and IR effects (Powell et al 2002; Lehmann et al 1999; Swerdlow et al 2008) [31–33], separate analyses were then pursued in male and female rats. Similar analyses were used to assess IR effects on startle magnitude on PULSE trials, NOSTIM trials, and startle habituation (startle magnitude on PULSE trials in blocks 1 vs. 4).…”

Section: Methodsmentioning

confidence: 99%

Forebrain gene expression predicts deficits in sensorimotor gating after isolation rearing in male rats

Swerdlow

Light

Trim

et al. 2013

Behavioural Brain Research

View full text Add to dashboard Cite

Compared to socially housed (SH) rats, adult isolation-reared (IR) rats exhibit phenotypes relevant to schizophrenia (SZ), including reduced prepulse inhibition (PPI) of startle. PPI is normally regulated by the medial prefrontal cortex (mPFC) and nucleus accumbens (NAC). We assessed PPI, auditory-evoked local field potentials (LFPs) and expression of 7 PPI- and SZ-related genes in the mPFC and NAC, in IR and SH rats. Buffalo (BUF) rats were raised in same-sex groups of 2–3 (SH) or in isolation (IR). PPI was measured early (d53) and later in adulthood (d74); LFPs were measured approximately on d66. Brains were processed for RT-PCR measures of mPFC and NAC expression of Comt, Erbb4, Grid2, Ncam1, Slc1a2, Nrg1 and Reln. Male IR rats exhibited PPI deficits, most pronounced at d53; male and female IR rats had significantly elevated startle magnitude on both test days. Gene expression levels were not significantly altered by IR. PPI levels (d53) were positively correlated with mPFC expression of several genes, and negatively correlated with NAC expression of several genes, in male IR but not SH rats. Late (P90) LFP amplitudes correlated significantly with expression levels of 6/7 mPFC genes in male rats, independent of rearing. After IR that disrupts early adult PPI in male BUF rats, expression levels of PPI- and SZ-associated genes in the mPFC correlate positively with PPI, and levels in the NAC correlate negatively with PPI. These results support the model that specific gene-behavior relationships moderate the impact of early-life experience on SZ-linked behavioral and neurophysiological markers.

show abstract

A novel rat strain with enhanced sensitivity to the effects of dopamine agonists on startle gating

Cited by 22 publications

References 58 publications

The effects of oxytocin and its analog, carbetocin, on genetic deficits in sensorimotor gating

The effects of oxytocin and its analog, carbetocin, on genetic deficits in sensorimotor gating

Intergenerational and parent of origin effects of maternal calorie restriction on Igf2 expression in the adult rat hippocampus

Forebrain gene expression predicts deficits in sensorimotor gating after isolation rearing in male rats

Contact Info

Product

Resources

About