Sprague Dawley rats from different vendors vary in the modulation of prepulse inhibition of startle (PPI) by dopamine, acetylcholine, and glutamate drugs

Abstract

Rationale: Rodent vendors are often utilized interchangeably, assuming that the phenotype of a given strain remains standardized between colonies. Several studies, however, have found significant behavioral and physiological differences between Sprague Dawley (SD) rats from separate vendors. Prepulse inhibition of startle (PPI), a form of sensorimotor gating in which a low-intensity leading stimulus reduces the startle response to a subsequent stimulus, may also vary by vendor. Differences in PPI between rat strains are well known, but divergence between colonies within the SD strain lacks thorough examination.

Objectives: We explored intrastrain variation in PPI by testing SD rats from two vendors: Envigo and Charles River (CR).

Methods: We selected drugs acting on four major neurotransmitter systems that have been repeatedly shown to modulate PPI: dopamine (apomorphine; 0.5, 1.5, 3.0 mg/kg), acetylcholine (scopolamine; 0.1, 0.5, 1.0 mg/kg), glutamate (dizocilpine; 0.5, 1.5, 2.5 mg/kg), and serotonin (2,5-Dimethoxy-4-iodoamphetamine, DOI; 0.25, 0.5, 1.0 mg/kg). We determined PPI and startle amplitude for each drug in male and female Envigo and CR SD rats.

Results: SD rats from Envigo showed dose-dependent decreases in PPI after apomorphine, scopolamine, or dizocilpine administration, without significant effects on startle amplitude. SD rats from CR were less sensitive to modulation of PPI and/or more sensitive to modulation of startle amplitude, across the three drugs.

Conclusions: SD rats showed vendor differences in sensitivity to pharmacological modulation of PPI and startle. We encourage researchers to sample rats from separate vendors before experimentation to identify the most suited source of subjects for their specific endpoints.

Keywords: Acetylcholine; Dopamine; Glutamate; PPI; Prepulse inhibition; Serotonin; Sprague Dawley rats; Startle amplitude; Startle response.

Fig. 1

Effects of apomorphine, scopolamine, and dizocilpine on prepulse inhibition. Percent PPI as a function of drug dose. Abscissae: doses of drugs in mg/kg, V denotes vehicle. Ordinates: percent prepulse inhibition of acoustic startle. Open symbols denote Charles River Sprague-Dawley rats and closed symbols denote Envigo Sprague-Dawley rats. *p<0.05, **p<0.01, ***p<0.001 vs. vehicle in each vendor group (Dunnett’s); †p<0.05 CR vs. Envigo at each dose (Holm-Sidak)

Fig. 2

Effects of apomorphine, scopolamine, and dizocilpine on startle amplitude. Startle amplitude during startle (“pulse”) alone trials, as a function of drug dose. Abscissae: doses of drugs in mg/kg, V denotes vehicle. Ordinates: amplitude of acoustic startle (arbitrary units). Open symbols denote Charles River Sprague-Dawley rats and closed symbols denote Envigo Sprague-Dawley rats. *p<0.05, **p<0.01, ***p<0.001 vs. vehicle in each vendor group; †p<0.05, ††p<0.01, †††p<0.001 CR vs. Envigo at each dose (Holm-Sidak)