Chromium picolinate reduces morphine-dependence in rats, while increasing brain serotonin levels

Abstract

Chromium is an essential trace element with anti-diabetic and anti-depressant effect; the latter is considered related to chromium properties of increasing brain serotonin. Cr³⁺ salts were shown to improve some forced swimming-parameters and to induce rewarding effects, which are additive to those of morphine, but Cr effect on addictive processes has not been tested.

Aim: The present study aimed to assess chromium picolinate (CrPi) influence on morphine-dependence in rats.

Matherial and methods: We used five groups of 10 rats. Groups 1 and 2 (controls) received saline, respectively CrPi, 0.01 mg/kg/day, for 10 days. In groups 3, 4 and 5 dependence was induced with progressively-increased morphine doses (from 5 - day 1-90 mg/kg/day - day 10, s.c.). Group 3 received only morphine, while groups 4 and 5 received CrPi, i.p., 10 and respectively 5 μg/kg/day, during the 10 days of dependence induction. On day 11, groups 3, 4, and 5 were administered 90 mg/kg morphine, and, 2 h later, all rats received naloxone, 2 mg/kg s.c., to precipitate withdrawal. We compared withdrawal intensity in group 3 vs. groups 4 and 5, assessing both individual symptoms and Gellert-Holtzman global withdrawal score. Upon rats sacrifice at the end of the experiments, brain serotonin (5HT) in certain areas and serum Cr were assessed.

Results: Some withdrawal signs were unequally influenced by CrPi: compulsive mastication was reduced by both CrPi doses (p < 0.05), while teeth chattering and grooming were significantly reduced only by the higher dose (p < 0.05). Withdrawal score was reduced by both CrPi doses: from 132.4 ± 9.87 - group 3 to 122.2 ± 6.47 - group 4 (p < 0.01 vs. group 3) and 124.1 ± 8.41 - group 5 (p < 0.05 vs. group 3). CrPi reduction of withdrawal is accompanied by increased brain 5 H T, mainly in the prefrontal cortex (646.3 ± 8.51 - group 3 vs. 661.5 ± 14.63 - group 4, p < 0.01 and 660.7 ± 14.01 pg/mg tissue - group 5, p < 0.05 vs. group 3). CrPi also increases brain 5 H T in non-dependent rats (prefrontal cortex: 541.6 ± 31.80, group 1 and 565.5 ± 16. 46 pg/mg tissue, group 2, p < 0.05). Administration of CrPi determined a dose-dependent increase of serum Cr.

Conclusions: Our study evidenced a slight, but significant reduction of morphine dependence in rats induced by chromium picolinate, accompanied by increased brain serotonin. This might be considered a supplementary evidence for chromium anti-depressant effect and its serotonin-mediated mechanisms.

Keywords: Chromium picolinate; Dependence; Morphine; Serotonin; withdrawal.