Rhodiola rosea L. extract and its active compound salidroside antagonized both induction and reinstatement of nicotine place prefrerence in mice

Abstract RATIONALE: Conventional pharmacological treatments for drug addiction aim to reduce three most important aspects: withdrawal syndrome, craving, and relapse. Pharmacological treatments currently available for the treatment of tobacco smoking are able to alleviate withdrawal symptoms but are not sufficiently effective in reducing craving and rarely effective to prevent relapse. Rhodiola rosea L., a well-known traditional oriental medicine with anxiolytic, antidepressive, antistress, and adaptogenic properties, has been recently shown to be effective in the prevention and treatment of nicotine-withdrawal symptoms. OBJECTIVES: The present study used the conditioned place preference (CPP) model to systematically investigate, in mice, the effects of a R. rosea L. extract (RHO) and its active compound salidroside (SDS), on the reinforcing properties of nicotine and their efficacy in the vulnerability to reinstatement. METHODS: To study the effects on the rewarding properties of nicotine, RHO (10, 15, and 20 mg/kg) and SDS (0.2 mg/kg) were tested both in the acquisition and expression of CPP induced by nicotine injection (0.5 mg/kg). Moreover, the efficacy of RHO and SDS in preventing relapse induced by nicotine priming (0.1 mg/kg, s.c.) and by restraint stress was also evaluated. RESULTS: Results showed the ability of RHO and salidroside to significantly reduce the rewarding properties of nicotine at all doses tested. RHO and SDS also suppressed both priming- and stress-induced reinstatement of CPP. CONCLUSIONS: The present study showed the positive effects of R. rosea L. in reducing rewarding properties and preventing relapse to nicotine and evidenced the important role of salidroside in the effects of the extract

Resiniferatoxin provides further evidence for a role of capsaicin-sensitive sensory neurons in the control of the kidney function.

Neonatal capsaicin treatment has been reported to impair the excretory function of the kidney in the rat. The present study evaluated the effect on urine excretion of the neurotoxin resiniferatoxin, an extremely potent structural analogue of capsaicin. Neonatal resiniferatoxin treatment (30 micrograms/kg) markedly reduced diuresis, natriuresis and kaliuresis in adult rats, in response to intragastric saline or water load and to furosemide administration, as well as in basal conditions. The effect of resiniferatoxin was more pronounced and long-lasting than that observed in previous studies following neonatal capsaicin treatment (50 mg/kg). On the other hand, administration of resiniferatoxin in adult rats did not affect urine excretion, suggesting that afferent fibers resistant to the neurotoxin treatment during adulthood, might be involved in the effect. The results of the present study are in keeping with the hypothesis that neuropeptides-containing capsaicin-sensitive sensory neurons might be involved in the physiological modulation of the kidney function

Effect of Pueraria lobata (Wild) on ethanol intake of alcohol-preferring rats.

The present study evaluated the effect of intraperitoneal injections of crude extracts of Radix pueraria (RP) on ethanol intake in genetically selected alcohol-preferring rats. Water and food sated rats were offered 10% ethanol intake for 10 h/day, during the dark phase of an inverse light-dark cycle. RP extracts reduced ethanol intake in alcohol-preferring rats. However, the dose of 75 mg/100 g body weight, that produced only minor behavioural alterations and did not modify total fluid intake, elicited only a modest attenuation (about 20%) of ethanol consumption. A more pronounced inhibition of ethanol intake was obtained following 150 and 300 mg/100 g, but these doses induced marked alterations of the gross behaviour in treated rats, which were rather immobile and apparently in a condition of malaise at least during the first hour after drug administration. Moreover, 150 mg/100 g produced a general inhibition of the ingestive behaviour, as shown by the finding that it inhibited water intake in water deprived rats and food deprived rats. Pronounced alterations on the gross behaviour were evident also in deprived rats, which were not offered 10% ethanol, thus indicating that they cannot be accounted for by an effect of RP on ethanol metabolis

Impairment of renal urinary excretion in neonatal, but not in adult capsaicin-pretreated rats.

The effect of saline and/or water load on diuresis, natriuresis and kaliuresis in control and in neonatal or adult capsaicin-pretreated awake rats has been assessed. Urine was collected by means of metabolic cages or intra-abdominally from a previously catheterized ureter. Neonatal but not adult capsaicin-pretreated animals exhibited a remarkable reduction in volume of urine output and in electrolytes excretion. This effect was more evident following saline as compared to water load. Similar results were also obtained when urine was directly collected from the ureters, suggesting that pharmacological ablation, at neonatal stage, of a subset of capsaicin-sensitive sensory nerves could impair the excretory kidney function

The ontogeny of the antidipsogenic effect of eledoisin and physalaemin in the rat

The ontogeny of the antidipsogenic effect of the tachykinins eledoisin and physalaemin was studied in 1- to 12-day-old Wistar rats. Both peptides inhibited drinking evoked by ICV angiotensin II, cell-dehydration or fluid deprivation. The effect of eledoisin appeared earlier than that of physalaemin (third v. sixth day) and was evoked by lower doses (10-100 ng/rat vs 330-1000 ng rat). The two tachykinins also inhibited milk intake, but this effect occurred only in the earliest days of neonatal life. The results confirm the specificity of the antitipsogenic effect of eledoisin and physalaemin and give further support to the hypothesis that brain tachykinins play a physiological role in the control of fluid intake

Effects of a Rhodiola rosea L. extract on the acquisition, expression, extinction, and reinstatement of morphine-induced conditioned place preference in mice

RATIONALE: Opioid addiction is a chronic, recurrent brain disease that is characterised by compulsive drug seeking and a high rate of relapse even after long periods of abstinence. Prevention of relapse is the primary goal of addiction treatment and is still the major limitation in drug therapy. OBJECTIVES: The present study investigated the effects of a Rhodiola rosea L. hydroalcoholic extract (RHO), a well-known traditional oriental medicine, on establishment and reinstatement of morphine-induced conditioned place preference (CPP) in mice. METHODS: CPP was induced by intraperitoneal injection of morphine (10 mg/kg) as an 8-day conditioning schedule. The effects of RHO on the rewarding properties of morphine were tested in mice receiving oral administration of RHO (10, 15, and 20 mg/kg) 60 min prior to each morphine injection (acquisition) or prior to the CPP test on day 9 (expression). Once established, CPP was extinguished by repeated testing, during which conditioned mice were injected daily with different doses of RHO. Finally, the efficacy of RHO in blocking reinstatement of CPP provoked by priming injections and physical stress was also evaluated. RESULTS: RHO administration showed dose dependency for prevention of establishment of CPP and was effective in facilitating extinction of morphine-induced CPP. RHO suppressed both priming- and stress-induced reinstatement of CPP in a dose-dependent manner. CONCLUSIONS: In conclusion, as RHO was effective for reducing craving and vulnerability to relapse, it might be a very effective natural remedy for the treatment of opioid addiction