Sensory and sensorimotor gating-disruptive effects of apomorphine in Sprague Dawley and Long Evans rats

Abstract

Rationale: Rat strains differ in sensitivity to the disruptive effects of dopamine agonists on sensorimotor gating, measured by prepulse inhibition (PPI) of startle. For example, Sprague Dawley (SD) rats are more sensitive to PPI-disruptive effects of apomorphine (APO) compared to Long Evans (LE) rats; F1 (SDxLE) and N2 generations exhibit intermediate phenotypes. We reported that APO increased S2/S1 ratios and reduced S1 amplitudes of the N40 event-related potential (ERP) in SD rats, suggesting that it reduced sensory gating and/or sensory registration. Here, we investigated whether SD and LE rats differ in sensitivity to APO effects on N40 gating or amplitude.

Methods: PPI and N40 gating were assessed contemporaneously in male SD and LE rats after APO, in a 4-day within-subject design.

Results: Compared to SD rats, LE rats were less sensitive to the PPI-disruptive effects of APO. APO increased S2/S1 ratios paralleled by a dose-dependent reduction in S1 amplitude; SD and LE rats did not differ significantly in this measure. No clear relationship was evident between APO effects on PPI and N40 gating, nor between APO effects on startle magnitude and S1 amplitude, across strains.

Conclusion: SD and LE rats differ in their sensitivity to the disruptive effects of dopamine receptor activation on sensorimotor gating (PPI) but not sensory gating (N40 suppression) or sensory registration (S1 amplitude). These data suggest differences in both the neural and genetic regulation of dopamine agonist effects on these measures.

Figure 1

Startle (A) and ERP (B) measures in SD and LE rats during drug-free test session. A. Significant strain difference in PPI (SD > LE; ** p < 0.0012) but not startle magnitude (inset). B. Near-significant difference in N40 gating ratio (SD > LE; p < 0.065) but not S1 or S2 amplitude (inset).

Figure 2

Grand average N40 ERP waveforms in SD and LE rats during drug-free test session, showing responses to S1 and "gated" S2 stimuli.

Figure 3

Startle (A) and ERP (B) measures in SD and LE rats during APO dose-response testing. A. Significant strain differences in post-vehicle levels of PPI (SD > LE (*)) and post-APO levels of PPI (LE > SD (#)) but not startle magnitude (inset). B. N40 gating ratio significantly increased by APO in both SD and LE strains, with no significant difference in either post-vehicle or post- APO levels of N40 gating. Inset shows APO-suppression of S1 amplitude in both SD and LE rats, with no strain differences in APO sensitivity. * p<0.015; ** p<0.008 vs vehicle, collapsed across strains.

Figure 4

Grand average N40 ERP waveforms in SD and LE rats during APO dose-response testing. Note progressive loss of S1 amplitude with increasing APO dose in both strains.