On again, off again effects of gonadectomy on the acoustic startle reflex in adult male rats

Abstract

Numerous studies have shown sex and/or estrous cycle differences in the acoustic startle reflex (ASR) and its prepulse inhibition (PPI) in humans and animals. However, few have examined the effects of hormone manipulations on these behaviors. This study paired gonadectomy (GDX) in adult male rats with testing for ASR and PPI at 2, 4, 9, 16, 23, 30 and 37 days after surgery. Initial studies of control, GDX and GDX rats given testosterone propionate revealed no group differences in PPI, but did reveal phasic facilitation of the ASR in GDX rats that was greatest on the first and final testing sessions and that was attenuated by testosterone. A second study addressing roles for estrogen and androgen signaling tested new control and GDX rats along with GDX rats given estradiol or the non-aromatizable androgen, 5-alpha-dihydrotestosterone and revealed no group differences in PPI, and increases in ASR in GDX rats that were largest during the first and final testing sessions and that were attenuated by both hormone replacements. However, while responses in GDX rats given testosterone were similar to those of controls, ASR in estradiol- and to a lesser extent in dihydrotestosterone-treated GDX rats were typically lower than in controls. This may suggest that hormone modulation of the ASR requires synergistic estrogen and androgen actions. In the male brain where this can be achieved by local steroid metabolism, the enzymes responsible, e.g., aromatase, could help identify loci in the startle circuitry that may be especially relevant for the hormone modulation observed.

Figure 1

Bar graphs showing mean group weights in grams (±SEM) of the bulbospongiosus muscles (BSM) dissected from each animal subject at the time of euthanasia. In A, mean BSM weights from the 8 control (CTRL), 8 gonadectomized (GDX) and 8 gonadectomized rats supplemented with testosterone propionate (GDX-TP) tested in the first series of experiments are shown. Among these groups, BSM weights were significantly lower (asterisk) in GDX rats compared to the CTRL and GDX-TP groups. In B, mean BSM weights in a second group of 8 CTRL and 8 GDX rats appear with weights of 8 gonadectomized rats supplemented with estradiol (GDX-E) and 8 with 5α-dihydrotestosterone (GDX-DHT); among these, weights in the GDX and GDX-E groups were significantly lower (asterisks) than those in the CRTL and GDX-DHT groups.

Figure 2

Line plots showing mean body weights (±SEM) of the control (CTRL), gonadectomized (GDX), and gonadectomized rats supplemented with 5α-dihydrotestosterone (GDX-DHT) or estradiol (GDX-E) measured immediately prior to sham-surgery or gonadectomy (Pre-Op.) and prior to each of the seven testing sessions (X-axis) in the second experiment. Body weights were similar in the CTRL, GDX and GDX-DHT groups on all testing days. However, weights in the GDX-E group were significantly different (asterisks) or nearly significantly different (pound sign) from CTRL on all testing days. The motor responses recorded from all of animal subjects in this experiment were adjusted using a correction factor that normalized each animal’s weight to the mean weight of the CTRL group measured on that day.

Figure 3

Bar graphs showing group mean (±SEM) responses during acoustic startle trials (A) and mean calculated group mean measures of prepulse inhibition (B) in control (CTRL white bars), gonadectomized (GDX, black bars) and gonadectomized rats given testosterone propionate (GDX-TP, gray bars). Values from testing that took place 2,4, 9, 16, 23, 30 and 37 days after sham surgery or GDX are shown (X-axes). Asterisks identify values that are significantly different from CTRL (p < 0.05), pound signs represent values where differences from the CTRL group approached significance (p < 0.09), ‘1’ marks values that are significantly different from GDX-TP, and ‘2’ represents values where differences from GDX-TP approach significance. Note that prepulse inhibition data from day 37 was aberrantly low (less than 20%) and was removed from the analysis.

Figure 4

Bar graphs showing group mean (±SEM) responses during acoustic startle trials (A) and calculated group mean measures of prepulse inhibition (B) in control (CTRL white bars), gonadectomized (GDX, black bars), gonadectomized rats given 5α-dihydrotestosterone (GDX-DHT, light gray bars) and gonadectomized rats givenestradiol (GDX-E, dark gray bars). Values from testing that took place 2,4, 9, 16, 23, 30 and 37 days after sham surgery or GDX are shown (X-axes). Asterisks identify values that are significantly different from CTRL (p < 0.05), pound signs represent values where differences from the CTRL group approached significance (p < 0.09), ‘1’ marks values that are significantly different from GDX-DHT , ‘2’ represents values where differences from GDX-DHT approach significance, and ‘3’ identifies values that are significantly different from GDX-E.