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

• DOI: 10.1007/s00213-023-06444-1
• Publication Date: 2023-08-14T19:23:17Z
• Authors: S.B. Caine; S. Plant; K. Furbish; M. Yerton; E. Smaragdi; B. Niclou; J.M. Lorusso; J.Y. Chang; C. Bitter; A. Basu; S. Miller; C.-Y. Huang; R. Komson; D. Liu; S. Behar; M. Thomsen
• Keywords: Male; Serotonin; Reflex, Startle; Apomorphine; PPI; Dopamine; 150; Scopolamine Derivatives; Glutamic Acid; Rats, Sprague-Dawley; Animals; Original Investigation; Prepulse Inhibition; Sprague Dawley rats; Startle response; Acetylcholine; 3. Good health; Rats; Pharmaceutical Preparations; Acoustic Stimulation; Prepulse inhibition; Dopamine Agonists; Startle amplitude; Female; Glutamate; Dizocilpine Maleate

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.