Nicotine limits avoidance conditioning with opioids without interfering with the ability to discriminate an opioid-interoceptive state.

Approximately 90 % of individuals undergoing treatment for opioid use disorder (OUD) report comorbid use of nicotine. As such, further investigation into underlying mechanisms contributing to the extreme comorbidity between nicotine and opioid use are warranted. Nicotine administration significantly escalates self-administration of opioids and this increase in motivational efficacy persists despite contingent punishment of opioid consumption. Additionally, both systemic and intra-insular administration of nicotine produces a rightward shift in the dose-response function in both morphine-induced conditioned place preference and taste avoidance paradigms, particularly at higher doses (5-20 mg/kg). Two possible interpretations arise from these outcomes. One is that nicotine may specifically affect learning about the malaise-inducing effects of morphine thus facilitating acceptance of higher doses of morphine. Another interpretation is that it more generally reduces sensitivity to the interoceptive effects of morphine such that higher doses are needed to produce comparable effects in nicotine-treated, relative to control, rats. To further address these possibilities, we asked whether nicotine administration interfered with the ability to discriminate the morphine interoceptive state, irrespective of its hedonic evaluation, at a dose that is impacted by nicotine in avoidance conditioning paradigms. First, we demonstrated that systemic nicotine pretreatment significantly attenuates taste avoidance induced by a low dose of morphine (3 mg/kg). Next, we used an occasion setting paradigm with this same dose of morphine to test whether systemic nicotine pretreatment interferes with the ability to discriminate between saline- and morphine-induced interoceptive states. Within this task, nicotine had no effect on the ability to effectively discriminate between the interoceptive effects of morphine and saline. Collectively, these data suggest that nicotine may be specifically altering the overall hedonic assessment of morphine perhaps by interfering with learning about its deleterious consequences.

Nicotine pre-treatment reduces sensitivity to the interoceptive stimulus effects of commonly abused drugs as assessed with taste conditioning paradigms.

BACKGROUND: Drug pre-exposure attenuates sensitivity to the interoceptive stimulus properties of additional subsequently administered drugs in drug-induced conditioned taste avoidance (CTA) and conditioned place preference (CPP) paradigms. Specifically, nicotine, commonly used in conjunction with other addictive substances, attenuates acquisition of ethanol and caffeine CTAs and morphine-induced CPP. METHODS: Because nicotine use is comorbid with a number of substance use disorders, we systematically examined the effects of nicotine pre-exposure on two different conditioning paradigms involving integration of the interoceptive stimulus properties of multiple commonly abused drugs, in male and female rats, designed to examine both the aversive and reinforcing properties of these drugs. RESULTS: Nicotine dose-dependently interfered with acquisition of CTA to passively administered morphine, ethanol, and cocaine, but not lithium chloride, demonstrating that the effects of nicotine are not simply a matter of reduced orosensory processing or an inability to learn such associations. Moreover, nicotine-treated rats required higher doses of drug in order to develop CTA and did not show increased acceptance of the taste of self-administered ethanol compared with saline-treated rats. CONCLUSIONS: These data demonstrate that nicotine pre-exposure attenuates sensitivity to the stimulus effects of multiple drugs in two conditioning paradigms, in a manner which is consistent with a reduced ability to integrate the interoceptive properties of abused drugs. Through reducing these stimulus properties of drugs of abuse, concomitant nicotine use may result in a need to increase either the frequency or strength of doses during drug-taking, thus likely contributing to enhanced addiction liability in smokers.

Examination of the perception of sweet- and bitter-like taste qualities in sucralose preferring and avoiding rats.

Sucralose avoiding rats detect a bitter-like taste quality in concentrations of sucralose that are strongly preferred over water by sucralose preferring rats. Here, we investigated whether sucralose preferrers (SP) also detect a bitter-like quality in sucralose that may be masked by an increased perception of sucralose's sweet-like quality. A microstructural analysis of sucralose intake revealed that, at concentrations they avoided in preference tests, sucralose avoiders (SA) consumed smaller and fewer bouts of sucralose than SP. Interestingly, the concentration-dependent increase in sucralose preference in SP was not associated with larger bouts or increased lick rate, two measures that are expected to increase with increasing perceived sweetness. This suggests that SP can detect an aversive quality in sucralose, but this perception of a presumably bitter-like quality may be masked by increased salience of a sweet-like quality that sustains high levels of intake in SP. Further evidence for increased sweet-taste perception in SP, relative to SA, was obtained in a second study in which SP consumed more of a palatable sweet-milk diet than SA. These are the first data to suggest that SP are not blind to the bitter-like quality in sucralose, and that there may be differences in sweet-taste perception between SP and SA.