Aims: 

In this study the effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on morphine withdrawal-induced anxiety and locomotor activity were investigated in mice.

Methods: 

Morphine withdrawal symptoms were tested in an open-field (Conducta). CFLP male mice were used. On first day, morphine pellets containing 35 mg of morphine were implanted subcutaneously (s.c.), control mice were sham-operated. Naloxone was used to precipitate morphine withdrawal syndrome. Morphine withdrawal mice treated with either PACAP (500 ng/2 ml, i.c.v.) or arteficial CSF (aCSF), control mice and morphine tolerant mice treated with aCSF (i.c.v.) once a day for 3 consecutive days. On fourth day, thirty minutes before open-field test mice were injected either PACAP or aCSF and five minutes before test mice treated with naloxone (0.2 mg/kg s.c.). Control mice and morphine tolerant mice given saline (s.c.) five minutes before test. The open-field test was assessed during a 15-min period.

Results: 

Morphine withdrawal mice receiving aCSF spent significantly more time in the central parts of the open field compared to morphine tolerant mice. Morphine withdrawal mice receiving PACAP showed significant increase in ambulation time and ambulation distance compared to morphine withdrawal mice receiving aCSF. PACAP alone had no significant effect on anxiety, but morphine withdrawal mice receiving PACAP spent more time in the central parts of the open field compared to morphine tolerant mice.

Conclusion: 

In our study, naloxone precipitated morphine withdrawal did not evoke anxiety, moreover, evoked anxiolytic behavior in mice. PACAP counteracted the locomotion decreasing effect of morphine withdrawal.

Support: 

ETT 355-08/2009 and TÁMOP 4.2.1B