Effects of naltrexone and cross-tolerance to morphine in a learned helplessness paradigm

Opiates have been implicated in learned helplessness (LH), a phenomenon known to be related to opiate stress-induced analgesia (SIA). In the present study, we investigated the role of opiates in the induction of LH and SIA under different conditions. Adult female Wistar rats were trained either by receiving 60 inescapable 1-mA footshocks (IS group, N = 114) or by confinement in the shock box (control or NS group, N = 92). The pain threshold of some of the animals was immediately evaluated in a tail-flick test while the rest were used 24 h later in a shuttle box experiment to examine their escape performance. The opiate antagonist naltrexone (0 or 8 mg/kg, ip) and the previous induction of cross-tolerance to morphine by the chronic administration of morphine (0 or 10 mg/kg, sc, for 13 days) were used to identify opiate involvement. Analysis of variance revealed that only animals in the IS group demonstrated antinociception and an escape deficit, both of which were resistant to the procedures applied before the training session. However, the escape deficit could be reversed if the treatments were given before the test session. We conclude that, under our conditions, induction of the LH deficit in escape performance is not opiate-mediated although its expression is opiate-modulated

The hyperinsulinemia produced by concanavalin A in rats is opioid-dependent and hormonally regulated

The present study examines the effect of concanavalin A (Con A) on the blood insulin and glucose levels of rats. Male and female rats treated with Con A (62.5-500 µg/kg) for three days showed a dose- and time-dependent hyperinsulinemia that lasted more than 48 h. Male rats were more sensitive to Con A. Thus, 6 h after treatment with Con A the circulating insulin levels in male rats had increased by 85% (control: 10.2 ± 0.9 mU/l and Con A-treated: 18.8 ± 1 mU/l) compared to only 38% (control: 7.5 ± 0.2 mU/l; Con A-treated: 10.3 ± 0.9 mU/l) in females. An identical response was seen after 12 h. Con A (250 µg/kg) produced time-dependent hypoglycemia in both sexes but more pronounced in males. There was no correlation between the hypoglycemia and hyperinsulinemia described above. The Con A-induced hyperinsulinemia in rats of both sexes was abolished in gonadectomized animals (intact males: +101 ± 17% vs orchiectomized males: -5 ± 3%; intact females: +86 ± 23% vs ovariectomized females: -18 ± 7.2%). Pretreating intact male and female rats with human chorionic gonadotropin also significantly inhibited the Con A-induced hyperinsulinemia. Estradiol (10 µg/kg, im) significantly blocked the Con A-induced increase in circulating insulin in male rats (101 ± 17% for controls vs 32 ± 5.3% for estradiol-treated animals, P<0.05) while testosterone (10 mg/kg, im) had no similar effect on intact female rats. Pretreating Con A-injected rats with opioid antagonists such as naloxone (1 mg/kg, sc) and naltrexone (5 mg/kg, sc) blocked the hyperinsulinemia produced by the lectin in males (control: +101 ± 17% vs naloxone-treated: +5 ± 14%, or naltrexone-treated: -23 ± 4.5%) and females (control: +86 ± 23% vs naloxone-treated: +21 ± 20%, or naltrexone-treated: -18 ± 11%). These results demonstrate that Con A increases the levels of circulating insulin in rats and that this response is opioid-dependent and hormonally regulated.