Figure 1.

Adenylyl cyclase activation or inhibition alters the development of morphine tolerance, but not antinociception. (a) Rats were pretreated with SQ22536 (200 ng/0.4 μl) or NKH477 (200 ng/0.4 μl) 20 min before saline (0.4 μl) or morphine (5 μg/0.4 μl). Morphine caused an increase in hot plate latency 30 min following injection regardless of pretreatment (Bonferroni post-hoc test compared with saline; *p<0.05). (b) Repeated microinjections twice a day for 3 days of morphine (5 μg/0.4 μl) or NKH477 (200 ng/0.4 μl) causes a rightward shift in the morphine dose response compared with saline controls. (c) Pretreatment with SQ22536 (200 ng/0.4 μl) in combination with morphine caused a leftward shift in the morphine dose–response curves compared with morphine alone (5 μg/0.4 μl). (d) Microinjection of SQ22536 (200 ng/0.4 μl) 20 min before the morphine microinjections on day 4 also reversed the shift in morphine pretreated rats.