Pigmentation, Anesthesia, Behavioral Factors, and Salicylate Uptake

Abstract

\s=b\In four experiments, 54 pigmented rats were used to examine the time course of sodium salicylate uptake in serum, cerebrospinal fluid, and perilymph. Subjects were tested under sodium pentobarbital anesthesia or while conscious. Compared with previously reported data from albino rats, pigmented subjects generally showed increased salicylate uptake. Moreover, the data suggested two different, time-dependent clearance mechanisms in conscious animals not observed in anesthetized rats.Daily injections of salicylate did not produce an accumulation of salicylate in serum. Systematically higher levels of salicylate were observed in perilymph compared with cerebrospinal fluid. Behavioral procedures, including water deprivation and conditioned suppression of ongoing drinking levels, had no effect on salicylate levels.

Salicylate-induced phantom auditory effects on reinforced behavior in pre- and postweanling rats

“…SEM = 1.4. These levels were in agreement with expectations based on peak salicylate levels obtained from adult rats 2-3 h after injection (Jastreboff, Issing. et al, 1988) and within the range observed in humans treated with salicylate (Mongan, Kelly.…”

“…In adult rats, there is no evident of long-term cumulative salicylate effects (Jastreboff, Hansen, Sasaki, & Sasaki, 1986;. Salicylate uptake in serum, cerebrospinal fluid, and perilymph reaches a maximum level in conscious, active adult rats about 2 h after injection, and salicylate levels tend to have a half life of about 6 h (Jastreboff, Issing, et al, 1988). Although we did not suspect that multiple injection effects would be different in preweanling pups, we nevertheless conducted an examination to determine whether chronic salicylate injections might have a cumulative effect on the behavior of young rats.…”

“…The experiments support the notion that the auditory system undergoes functionally important change at around 15-16 days of age.We have reported behavioral evidence from adult pigmented rats that phantom auditory sensations induced by salicylate injection can influence the behavior of rats trained to associate periods of silence with aversive events, in a manner similar to that predicted if the animals were perceiving a sound (Jastreboff, Brennan, Coleman, & Sasaki, 1988). In the adult paradigm, sodium salicylate was injected at dose levels suggested by studies that delineated its uptake in blood serum, cerebrospinal fluid, and the perilymph, under a variety of metabolic states and during various behavioral tasks (Jastreboff, Issing, Brennan, & Sasaki, 1988). Our initial concern in this research was to establish an animal model of phantom auditory perception, or tinnitus, which is reported in humans as sound perceived in the absence of any external auditory stimulus.…”

Too much of a good thing: Long-term treatment with salicylate strengthens outer hair cell function but impairs auditory neural activity

“…In more recent work, we have shown that 1.4 mM of sodium salicylate causes significant loss of SGN in cochlear cultures; cell loss is preceded by soma shrinkage, a morphological feature of apoptosis, and caspase activation (Wei, 2009). The 1.4 mM dose used in our culture is clinically relevant since it is similar to the concentration seen in the cerebrospinal fluid and perilymph of animals that develop salicylate-induced tinnitus and hearing loss (Jastreboff et al , 1986; Jastreboff et al , 1988b). Our results plus previous in vitro studies suggest that further studies are needed to determine if high-dose, long term salicylate treatment damages SGN.…”

Animal Models of Subjective Tinnitus

“…90 minutes after an i.p. injection of 350 mg/kg sodium salicylate (corresponding to 300 mg/kg salicylic acid), the salicylate serum level in the rat was 625 mg/L [106]. For the dosage of 100 mg/kg inducing reliable tinnitus in the rat, the expected salicylate serum concentration is approiamtely 56 mg/L.…”