Influences of CCK-8 on expressions of apoptosis-related genes in prefrontal cortex neurons of morphine-relapse rats

Neurosci Lett. 2016 Sep 19:631:115-121. doi: 10.1016/j.neulet.2016.08.028. Epub 2016 Aug 17.

Abstract

In order to elucidate the influences of CCK-8 on expressions of apoptosis-related genes, Bax, Bcl-2 and Caspase-3, of prefrontal cortex neurons in morphine-relapse rats, an effective, successful morphine-relapse-rat model using the conditioned place preference (CPP) under CCK-8 (0.01, 0.1 and 1.0μg, i.c.v) intervention was established. The prefrontal cortexes were made into slices with the cellular plasmas immunohistochemically stained. The expressions of Bax, Bcl-2, Caspase-3 of neurons were evaluated through their scores, and each corresponding ratio of Bax and Bcl-2 (Bax/Bcl-2) was also computed. The results showed that the expression of Bcl-2 was very weak and those of Bax and Caspase-3 were hardly seen in group normal saline; the expressions of Bax and Caspase-3 were strong and that of Bcl-2 was weak in group morphine and compared to group normal saline, there were significant differences (P<0.05); the expressions of Bax, Caspase-3 and the ratios of Bax/Bcl-2 have a gradually-decreased trend in the sequence of group 0.01μg, group 0.1μg and group 1.0μg, but the expression of Bcl-2 has an opposite trend in the same sequence, and compared to group morphine, there were significant differences (P<0.05) excluding group 0.01μg. So we draw a conclusion that CCK-8 (0.1 and 1.0μg, i.c.v) could protect neurons of prefrontal cortex through up-regulating the expression of Bcl-2, down-regulating those of Bax and Caspase-3 and reducing Bax/Bcl-2 ratio in the model of morphine-relapse rats.

Keywords: Bax; Bcl-2; Caspase-3; Cholecystokinin-8; Morphine; Morphine relapse.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / genetics*
  • Caspase 3 / metabolism
  • Conditioning, Classical / drug effects
  • Conditioning, Classical / physiology
  • Male
  • Morphine / administration & dosage*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Wistar
  • Recurrence
  • Sincalide / administration & dosage*
  • Sincalide / physiology
  • bcl-2-Associated X Protein / metabolism

Substances

  • Bax protein, rat
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Morphine
  • Casp3 protein, rat
  • Caspase 3
  • Sincalide