Cocaine decreases saccharin preference without altering sweet taste sensitivity

Abstract

In rodents, saccharin consumption is suppressed when the sweet taste stimulus is paired with moderate doses of cocaine. Several hypotheses have been used to explain the seemingly contradictory effect of decreased consumption of a normally preferred substance following a highly rewarding drug. A common theme across these hypotheses is that saccharin is interpreted as less rewarding after cocaine pairing. We considered the alternative possibility that suppression is caused not by a change in reward circuitry, but rather by a change in taste detection, for instance by altering the afferent taste response and decreasing sensitivity to sweet taste stimuli. To evaluate this possibility, we measured saccharin taste sensitivity of mice before and after a standard cocaine-pairing paradigm. We measured taste sensitivity using a brief-access lickometer equipped with multiple concentrations of saccharin solution and established concentration-response curves before and after saccharin-cocaine pairing. Our results indicate that the EC50 for saccharin was unaltered following pairing. Instead, the avidity of licking saccharin, an indicator of motivation, was depressed. Latency to first-lick, a negative indicator of motivation, was also dramatically increased. Thus, our findings are consistent with the interpretation that saccharin-cocaine pairing results in devaluing of the sweet taste reward.

Cocaine-induced loss of LTD and social impairments are restored by fatty acid amide hydrolase inhibition

“…Instead, we hypothesize that cocaine exposure induces long-lasting neuroplastic adaptations in the mesocorticolimbic system, responsible for natural reward processing, leading to the observed changes in saccharin preference. In line with this, previous studies have extensively documented that pairing cocaine with saccharin dramatically decreases saccharin intake 12 , 13 , 21 – 23 . This effect appears to be due to a decrease in the perceived value of saccharin as a reward, rather than an impairment in sweet taste sensitivity 13 .…”

“…However, it is unclear whether a single cocaine administration can induce behavioral changes beyond its acute effects. For example, repeated pairings of saccharin with cocaine decrease saccharin consumption 12 , 13 . Similarly, both acute 14 – 16 and chronic 17 cocaine use in rodents reduces social interaction during drug use and even after one day of withdrawal from repeated exposure 18 .…”

Experience-dependent plasticity of gustatory insular cortex circuits and taste preferences

“…1g, right; water: naïve n=1496 licks, EE n=1405 licks, U=927887, p=8.2×10 -10 ; sucrose: naïve n=2324 licks, EE n=3583 licks, U=3872876, p=5.2×10 -5 , Mann-Whitney U test). As bout size is directly linked to palatability (Davis et al, 1999; Johnson, 2018; Volcko et al, 2020), and accumulation of licks is evidence of increased avidity to sucrose (Roebber et al, 2015), these results indicate that mice in the EE group perceived sucrose as more palatable than naïve mice.…”

Experience-dependent plasticity of gustatory insular cortex circuits and taste preferences

“…1F , right; left, water: naïve, n = 1496 licks; EE, n = 1405 licks; U = 927,887, P = 8.2 × 10 −10 ; right, sucrose: naïve, n = 2324 licks; EE, n = 3583 licks; U = 3,872,876, P = 5.2 × 10 −5 ; Mann-Whitney U test). As bout size is directly linked to palatability ( 22 ) and accumulation of licks is evidence of increased avidity to sucrose ( 23 ), these results indicate that mice in the EE group perceived sucrose as more palatable than naïve mice.…”

“…Wild-type C57Bl/6 mice were purchased from Charles River Laboratories to arrive either as adults or as litters, including the lactating mother and pups at P5. PV-cre ( 23 ) (JAX stock no. 017320) and Ai14 ( 24 ) (RRID: IMSR_JAX:007908 ) were ordered from the Jackson Laboratory and crossed in our animal facility.…”