Eduardo Cuenca

Effects of yohimbine on morphine analgesia and physical dependence in the rat.

The effects of yohimbine on morphine analgesia and on the development of opiate physical dependence were studied to find out more about the involvement of alpha 2-adrenergic mechanisms in opioid actions. Male Sprague-Dawley rats (250-300 g) were used. The acute effect of morphine (5 mg/kg i.p.) in the tail-flick test was reduced significantly by pretreatment with a single dose of yohimbine (2 mg/kg i.p.). Alone yohimbine, produced a slight hyperalgesia. Animals treated with a sustained-release preparation of morphine (300 mg/kg s.c.) showed the same sensitivity to opiate analgesia 72 h later whether they were treated concomitantly with yohimbine or not, but they exhibited fewer withdrawal symptoms upon naloxone injection after yohimbine (2 or 4 mg/kg i.p. 24, 28, 48 and 52 h after the start of systemic morphine treatment). The results obtained confirm previous data on the effects of yohimbine on morphine analgesia and reveal the importance of alpha 2-adrenergic activation in the development of opioid physical dependence.

Yohimbine reduces morphine tolerance in guinea-pig ileum

Opiates are known to inhibit electrically-evoked twitches of longitudinal muscle-myenteric plexus strips from guinea-pig ileum. When this preparation was incubated with morphine for 1 h tolerance developed to the inhibitory effect, since dose-response curves were shifted to the right. In the present study, the effects of alpha-2 adrenergic agents on the tolerance induced by morphine in this preparation was investigated. Addition of yohimbine 10 microM (but not 0.1 or 1 microM) to the incubating medium reduced the magnitude of opiate tolerance. This effect did not appear in the presence of the alpha-2 agonists clonidine or guanfacine (10 microM). Our results provide evidence of the longitudinal muscle-myenteric plexus as a useful model for the study of the relationship between morphine tolerance and alpha-2 adrenergic mechanisms.

Evolution of the management of depression in Spain from the psychiatrist's perspective. A comparative analysis: 1997 vs 1982.

The main problem of depression is not only the high prevalence of the disorder but also its serious consequences on the patients quality of life and the associated social costs in terms of health care resource utilization and productivity losses. In recent years, there has been a considerable improvement in the knowledge of depression from the pathogenic, clinical and therapeutic perspectives. The present study analyzes whether such advances are reflected in a positive evolution of the treatment of depression in Spain. To this effect we have contrasted the results of two socio-sanitary studies published in this country: the White Book editions of 1982 and 1997 (WB82 and WB97, respectively). From the methodological perspective, the physician selection criteria employed were very uniform (structured questionnaires delivered to 128 (WB82) and 300 (WB97) randomly selected psychiatrists). The origin of patients consulting for specialized care has varied over this 15-year period. In effect, WB82 patients were essentially referred by friends (87.5%) and from the primary care setting (44.5%), whereas in the WB97 study referral from primary care predominated (50.1%), followed by the patients personal decision (24.8%). In turn, 40.7% and 51.7% of the psychiatrists in WB97 respectively considered the diagnostic and therapeutic means available in primary care to be insufficient. The priorities for improving patient quality of life, as reflected by both editions of the study, were the training of primary care physicians and the adequate provision of means in the mental health care centers. On the other hand, fewer problems for establishing a correct diagnosis were referred in the 1997 edition of the study (28.7%) than in 1982 (48.4%). In this sense, the main problem reported in WB82 was the lack of specialized training, whereas the masking of depression by some other disease process or symptoms was the main problem in WB97 (67.6% vs 21.1% according to WB82). The main symptoms upon which the diagnosis of depression are based do not seem to have evolved much in the past 15 years. The most frequently cited manifestations were a worsening of mood, loss of interest and leisure capacity, sleep alterations and diminished vitality. A comparative analysis of the therapeutic resources used was not possible, for prior to 1982 the only drugs available to physicians were the classical tricyclic agents and some MAO inhibitors; the selective serotonin reuptake inhibitors (SSRIs) - possibly the greatest advance in the treatment of depression in these 15 years - had not yet been introduced. Nevertheless, it should be pointed out that 98% of the psychiatrists consulted in WB97 considered pharmacologic treatment to be the most widely adopted form of management once depression has been diagnosed.

Effect of morphine and acetylcholine on contractile activity and cyclic AMP in guinea-pig ileum

Neither acute nor prolonged exposure to morphine altered cAMP content or spontaneous movements of longitudinal muscle-myenteric plexus strips of the guinea-pig ileum. By contrast, exogenous acetylcholine or electrical stimulation of the strips elicited both a decrease of cAMP concentration and a twitch response. Atropine blocked the effects of stimulation on these parameters. Addition of morphine to electrically stimulated strips inhibited the twitch response but did not affect cAMP levels. Incubation with morphine led to the development of tolerance to the inhibitory effect on twitch activity and prevented the fall in cAMP normally elicited by electrical stimulation. These results suggest that muscarinic activation is associated with a reduction of cAMP content, an effect which would be impaired in opiate-tolerant tissues.