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 shutttle 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.

Chronic but not acute Li+ treatment prevents behavioral depression in rats

The effect of lithium administration on the learned hellessness model of depression was investigated. Female Wistar rats (190-210g) received either tap water alone (N=156) or 20 mM LiCL, provided chronically (30 days; N = 127) or acutely (5 days; N = 22), in the drinking water. Three days before the end od treatment, each group was divided into two subgroups which received either inescapable shock (IS) or no shock (NS) treatment in shuttle boxes. All groups were subsequenty submitted to an escape test on the following day and then sacrificed one day after the escape test, when blood samples were taken to measure serum Li+, Na+ and K+ concentrations by flame photometry. There were no significant differences in serum Na+ amongst the 4 groups. chronically treated NS and IS rats both presented an increase in serum K+ compared to the control rats. The IS and not the NS chronically treated rats presented increased serum Li+ levels which cannot be accounted for in terms of differences in Li+ intake. The IS group treated chronically with lithium had a better escape performance than the IS group receiving either tap water or acute Li+ administration. We conclude that chronic but not acute Li+ treatment at a serum level within the prophylactic range (0,5 mEq) is able to prevent learned helplessness in the rat. These results agree with the data obtained in clinical practice indicating that li+ is only effective after chronic administration and that Li+ - induced hyperkalemia is a side effect

Lithium treatment prolongs shock-induced hypoalgesia

We have investigated the effect of chronic lithium (Li+) treatment on stress-induced hypoalgesia, a phenomenon known to be dependent on the activation and sensitization of the central opioid system. Adult female Wistar rats received either 20 mM LiCl in the drinking water (serum level of 0.5 mEq/l,N = 110) or tap water (controls N = 113) for 28 days. The rats were divided into three subgroups and were trained either by receiving 60 inescapable 1-mA footshocks (IS) while yoked to a escapable (ES) group, or by confinement (NS) to the shock box. As a control for the activation of the opioid system, we included rats injected with 0.9 percent saline (N = 24) or morphine (4 mg/kg, sc, N =20) before confinement. Twenty-four hours later, the rats (N = 187) were either submitted to five inescapable (1 s,0.6 mA) footshocks (shock reexposure) or received no shocks over the same period (N = 80). The pain threshold was estimated using a tail-flick apparatus after the training session and immediately after the shock reesposure. ANOVA followed by duncan's test indicated that hypoalgesia was produced soon after the training session in the morphine and shocked groups and persisted in the Li+-IS group for up to three days. Hypoalgesia was reinstated in the control IS and morphine groups by reexposure to the shochs, but was not modified in the Li+-IS groups. We conclude that Li+ treatment prolongs the hypoalgesia induced by inescapable shocks