Escalating morphine dosing in HIV-1 Tat transgenic mice with sustained Tat exposure reveals an allostatic shift in neuroinflammatory regulation accompanied by increased neuroprotective non-endocannabinoid lipid signaling molecules and amino acids

Table 1 Morphine-induced antinociceptive tolerance (%MPE) in the tail-flick (mean ± SEM, n = 7–9 per group) and hot-plate (mean ± SEM, n = 3–4 per group) assays

Assay	Mouse	Repeated saline ED₅₀ (95% CI)	Repeated morphine ED₅₀ (95% CI)	Sig.	Potency ratio (95% CI)
Tail flick	Tat(−)	8.6 (7.0–10.5)	26.6 (20.3–34.8)	*	3.2 (2.3–4.4)^a
Tail flick	Tat(+)	7.8 (6.2–9.8)	91.3 (60.7–137.4)¹	*	6.7 (4.6–10.8)^a^§
Hot plate	Tat(−)	6.1 (4.3–8.7)	14.5 (8.1–26.1)	n.s.	2.7 (0.5–8.7)
Hot plate	Tat(+)	5.4 (4.2–7.0)	23.0 (11.4–46.3)	*	4.4 (0.7–28.9)

ED50 values (mg/kg) and potency ratio values are derived from acute cumulative dose-response curves obtained for repeated short-term saline- and morphine-exposed mice.; n.s. not significant; *p < 0.05 saline vs. corresponding morphine group; ^ap < 0.05; ^§Indicates significance from Tat(−) in the tail-flick assay based on non-overlapping 95% CI. Note, as the potency ratio of 6.7 is based on an estimated ED₅₀ value caution should be exercised when interpreting the data. CI confidence interval
¹Estimated ED₅₀

ISSN: 1742-2094