Effects of the kappa opioid agonist U50,488 and the kappa opioid antagonist nor-binaltorphimine on choice between cocaine and food in rhesus monkeys

Abstract

These results suggest that continuous treatment with U50,488 produces a kappa receptor-mediated increase in the relative reinforcing effects of cocaine in comparison with food.

Blockade of kappa opioid receptors attenuates the development of depressive-like behaviors induced by cocaine withdrawal in rats

“…Further studies showed that despite a lack of effect on the expression of already-developed cocaine-induced anhedonia, norBNI completely prevented cocaine withdrawal-induced depressive-like effects upon exposure to a new stressor—forced swimming—suggesting a dissociation in the neurobiological mechanisms subservinganhedonia and increased stress sensitivity after binge cocaine. These findings are consistent with previous studies linking KORs and addictive behaviors (Beardsley et al, 2005; Jackson et al, 2010; Negus, 2004; Walker and Koob, 2007; Wee et al, 2009). In addition, they are broadly consistent with previous work showing that treatment with KOR antagonists before the first exposure to a stress—in this case, cocaine withdrawal or forced swim stress—is highly effective at blocking stress-induced behavioral adaptations (see Knoll and Carlezon Jr, 2010; Knoll et al, 2007).…”

Blockade of kappa opioid receptors attenuates the development of depressive-like behaviors induced by cocaine withdrawal in rats

“…Further studies showed that despite a lack of effect on the expression of already-developed cocaine-induced anhedonia, norBNI completely prevented cocaine withdrawal-induced depressive-like effects upon exposure to a new stressor—forced swimming—suggesting a dissociation in the neurobiological mechanisms subservinganhedonia and increased stress sensitivity after binge cocaine. These findings are consistent with previous studies linking KORs and addictive behaviors (Beardsley et al, 2005; Jackson et al, 2010; Negus, 2004; Walker and Koob, 2007; Wee et al, 2009). In addition, they are broadly consistent with previous work showing that treatment with KOR antagonists before the first exposure to a stress—in this case, cocaine withdrawal or forced swim stress—is highly effective at blocking stress-induced behavioral adaptations (see Knoll and Carlezon Jr, 2010; Knoll et al, 2007).…”

Effects of repeated nalfurafine and VZTK35 treatments on fentanyl/cocaine mixture self-administration in a rat drug-vs.-food choice procedure

“…Thus, the VZTK35 effects on fentanyl/cocaine choice seem to be driven mostly by VZTK35 effects on cocaine choice rather than fentanyl choice. These results may indicate that NLF and VZTK35 treatment increases the ability of cocaine but not fentanyl to compete with food as a reinforcer, consistent with a previous study on KOR agonist administration during cocaine-vs.-food choice ( Negus 2004 ). Further study is needed to determine whether this shift in relative reinforcing efficacy is due to an underlying change in food or cocaine reinforcing efficacy.…”

“…VZTK35 and NLF pretreatments also significantly increased cocaine choice, but not fentanyl choice. The VZTK35 and NLF results are consistent with a previous nonhuman primate study examining treatment with the KOR agonist U50,488 on cocaine choice as well as the effect of NLF pretreatment on cocaine self-administration in mice ( Negus 2004 ; Dunn et al 2020 ). Furthermore, the present repeated 5-day NLF results were also consistent with published acute NLF pretreatment effects on fentanyl choice and extend those results to repeated NLF dosing regimens ( Townsend 2021a ).…”

Effects of the kappa opioid receptor antagonist nor‐binaltorphimine (nor‐BNI) on cocaine versus food choice and extended‐access cocaine intake in rhesus monkeys

“…The lack of nor-BNI effect on cocaine vs. food choice under extended cocaine access conditions was consistent with our previous study determining nor-BNI effects on cocaine choice under limited cocaine access conditions (Negus 2004). In the previous study, 3.2 mg/kg nor-BNI was sufficient to block increases in cocaine vs. food choice produced by treatment with an exogenous KOR agonist (Negus 2004), and 3.2 mg/kg nor-BNI was also sufficient to antagonize other KOR agonist-induced behavioral effects in rhesus monkeys (Butelman et al 1993; Ko et al 2003).…”

Blockade of kappa opioid receptors attenuates the development of depressive-like behaviors induced by cocaine withdrawal in rats

“…Further studies showed that despite a lack of effect on the expression of already-developed cocaine-induced anhedonia, norBNI completely prevented cocaine withdrawal-induced depressive-like effects upon exposure to a new stressor—forced swimming—suggesting a dissociation in the neurobiological mechanisms subservinganhedonia and increased stress sensitivity after binge cocaine. These findings are consistent with previous studies linking KORs and addictive behaviors (Beardsley et al, 2005; Jackson et al, 2010; Negus, 2004; Walker and Koob, 2007; Wee et al, 2009). In addition, they are broadly consistent with previous work showing that treatment with KOR antagonists before the first exposure to a stress—in this case, cocaine withdrawal or forced swim stress—is highly effective at blocking stress-induced behavioral adaptations (see Knoll and Carlezon Jr, 2010; Knoll et al, 2007).…”

Effects of repeated nalfurafine and VZTK35 treatments on fentanyl/cocaine mixture self-administration in a rat drug-vs.-food choice procedure

“…Thus, the VZTK35 effects on fentanyl/cocaine choice seem to be driven mostly by VZTK35 effects on cocaine choice rather than fentanyl choice. These results may indicate that NLF and VZTK35 treatment increases the ability of cocaine but not fentanyl to compete with food as a reinforcer, consistent with a previous study on KOR agonist administration during cocaine-vs.-food choice ( Negus 2004 ). Further study is needed to determine whether this shift in relative reinforcing efficacy is due to an underlying change in food or cocaine reinforcing efficacy.…”

“…VZTK35 and NLF pretreatments also significantly increased cocaine choice, but not fentanyl choice. The VZTK35 and NLF results are consistent with a previous nonhuman primate study examining treatment with the KOR agonist U50,488 on cocaine choice as well as the effect of NLF pretreatment on cocaine self-administration in mice ( Negus 2004 ; Dunn et al 2020 ). Furthermore, the present repeated 5-day NLF results were also consistent with published acute NLF pretreatment effects on fentanyl choice and extend those results to repeated NLF dosing regimens ( Townsend 2021a ).…”

Effects of the kappa opioid receptor antagonist nor‐binaltorphimine (nor‐BNI) on cocaine versus food choice and extended‐access cocaine intake in rhesus monkeys

“…The lack of nor-BNI effect on cocaine vs. food choice under extended cocaine access conditions was consistent with our previous study determining nor-BNI effects on cocaine choice under limited cocaine access conditions (Negus 2004). In the previous study, 3.2 mg/kg nor-BNI was sufficient to block increases in cocaine vs. food choice produced by treatment with an exogenous KOR agonist (Negus 2004), and 3.2 mg/kg nor-BNI was also sufficient to antagonize other KOR agonist-induced behavioral effects in rhesus monkeys (Butelman et al 1993; Ko et al 2003).…”

Blockade of kappa opioid receptors attenuates the development of depressive-like behaviors induced by cocaine withdrawal in rats

“…Further studies showed that despite a lack of effect on the expression of already-developed cocaine-induced anhedonia, norBNI completely prevented cocaine withdrawal-induced depressive-like effects upon exposure to a new stressor—forced swimming—suggesting a dissociation in the neurobiological mechanisms subservinganhedonia and increased stress sensitivity after binge cocaine. These findings are consistent with previous studies linking KORs and addictive behaviors (Beardsley et al, 2005; Jackson et al, 2010; Negus, 2004; Walker and Koob, 2007; Wee et al, 2009). In addition, they are broadly consistent with previous work showing that treatment with KOR antagonists before the first exposure to a stress—in this case, cocaine withdrawal or forced swim stress—is highly effective at blocking stress-induced behavioral adaptations (see Knoll and Carlezon Jr, 2010; Knoll et al, 2007).…”

Effects of repeated nalfurafine and VZTK35 treatments on fentanyl/cocaine mixture self-administration in a rat drug-vs.-food choice procedure

“…Thus, the VZTK35 effects on fentanyl/cocaine choice seem to be driven mostly by VZTK35 effects on cocaine choice rather than fentanyl choice. These results may indicate that NLF and VZTK35 treatment increases the ability of cocaine but not fentanyl to compete with food as a reinforcer, consistent with a previous study on KOR agonist administration during cocaine-vs.-food choice ( Negus 2004 ). Further study is needed to determine whether this shift in relative reinforcing efficacy is due to an underlying change in food or cocaine reinforcing efficacy.…”

“…VZTK35 and NLF pretreatments also significantly increased cocaine choice, but not fentanyl choice. The VZTK35 and NLF results are consistent with a previous nonhuman primate study examining treatment with the KOR agonist U50,488 on cocaine choice as well as the effect of NLF pretreatment on cocaine self-administration in mice ( Negus 2004 ; Dunn et al 2020 ). Furthermore, the present repeated 5-day NLF results were also consistent with published acute NLF pretreatment effects on fentanyl choice and extend those results to repeated NLF dosing regimens ( Townsend 2021a ).…”

Effects of the kappa opioid receptor antagonist nor‐binaltorphimine (nor‐BNI) on cocaine versus food choice and extended‐access cocaine intake in rhesus monkeys

“…The lack of nor-BNI effect on cocaine vs. food choice under extended cocaine access conditions was consistent with our previous study determining nor-BNI effects on cocaine choice under limited cocaine access conditions (Negus 2004). In the previous study, 3.2 mg/kg nor-BNI was sufficient to block increases in cocaine vs. food choice produced by treatment with an exogenous KOR agonist (Negus 2004), and 3.2 mg/kg nor-BNI was also sufficient to antagonize other KOR agonist-induced behavioral effects in rhesus monkeys (Butelman et al 1993; Ko et al 2003).…”