Alcohol and drug research最新文献

Although the morphological teratogenic actions of ethanol have been well established in mice, studies on the behavioral teratogenic effects of alcohol have been primarily conducted with rats. The purpose of this study was to examine the behavioral effects of prenatal alcohol exposure in C57 mice, a strain known to be highly sensitive to the teratogenic actions of ethanol. Pregnant mice were administered a liquid diet containing 25% ethanol-derived calories (EDC) from day 5 through day 18 of gestation. Control animals were pair-fed an isocaloric 0% EDC diet during the same period of time, with sucrose substituted for ethanol. At 23 days of age, offspring were tested for spontaneous locomotor activity in an open field. At 70 days of age, different offspring were tested in a shuttle-avoidance task. The results demonstrated that the 25% EDC progeny were more active than controls. In addition, prenatal alcohol exposure produced a deficit in acquisition and performance of a shuttle-avoidance task. Alcohol-treated offspring made fewer avoidance responses and required more trials to reach a criterion performance of 10/10 avoidances consecutively followed by at least 9/10 avoidances. These results importantly contribute to the development of an animal model of Fetal Alcohol Syndrome in which both the behavioral and morphological consequences of prenatal alcohol exposure may be assessed in the same species.

The effects of sodium fluoride (NaF) and ethanol on adenylate cyclase activity were investigated in mouse and rat striatum and cerebral cortex. In a crude homogenate of striatum, NaF (10 mM) had no effect on adenylate cyclase activity even though guanyl-5'-yl-imidodiphosphate (GppNHp) increased enzyme activity by two-fold. Addition of 300 mM ethanol increased basal and GppNHp-stimulated activity and allowed expression of an effect of NaF. Stimulation of adenylate cyclase activity by NaF was also observed after sedimentation and resuspension of membranes. Readdition of the supernatant to washed membranes caused a decrease in maximal NaF-stimulated activity without any change in the concentration of NaF required for half-maximal stimulation. The inhibitory effect of the supernatant was resistant to heat but was eliminated by the addition of ethanol or perchloric acid. Inhibition of NaF-stimulated adenylate cyclase activity in striatal tissue was also observed when assays were carried out in the presence of a 20,000 X g supernatant prepared from cerebral cortex. NaF-stimulated activity in cortical tissue was, on the other hand, enhanced in the presence of a 20,000 X g supernatant prepared from either cortex or striatum. This suggests that there is a basic difference between the adenylate cyclase systems of these tissues.

In male rats given 6.0-8.0 g/kg of ethanol/day via gastric intubation, footshock stress accelerated the development of functional tolerance to ethanol (ethanol-induced hypothermia and motor impairment on a dowel task). A primarily psychological stressor (observing other rats that were being shocked) may have retarded tolerance development as subjects in this condition showed no development of functional tolerance. Nonstressed subjects developed tolerance more slowly and required a higher daily dose of ethanol to develop tolerance than shock stressed subjects. Conditioned responses to the drug administration procedure did not appear to play a role in the development of tolerance.

Delta-9-tetrahydrocannabinol, the principal psychoactive ingredient in cannabis extract, and cannabis extract containing an equivalent amount of delta-9-tetrahydrocannabinol were administered to different groups of pregnant mice on gestation days 7-15 inclusive. There was a significant dose-related increase in resorptions but no significant difference between compounds in resorption rate, nor was there any significant interaction between drug and dosage. The results suggest that compounds in cannabis extract do not modify the actions of delta-9-tetrahydrocannabinol on resorption rate.

Cyclazocine is a benzomorphan which, in addition to more classical opiate properties, binds to the sigma opiate receptor site. Recently, it has been suggested that the sigma opiate receptor is identical to the binding site responsible for the actions of phencyclidine (PCP). Since the electrophysiological actions of PCP have already been demonstrated on rat cerebellar Purkinje neurons, the effects of cyclazocine were also studied in this system with the goal of comparing the electrophysiological effects of cyclazocine to those of PCP. Cyclazocine inhibited the spontaneous firing rates of Purkinje neurons. These responses were stereospecific and qualitatively appeared similar to the effects of PCP. Antipsychotic drugs, haloperidol and fluphenazine, partially antagonized the actions of cyclazocine, suggesting a catecholaminergic involvement similar to the mechanism proposed for PCP. Unlike PCP, the effects of cyclazocine were also partially reversed by the opiate antagonist, naloxone. Taken together, these results suggest that in the rat cerebellum cyclazocine may be interacting with at least two receptor mechanisms: a naloxone-sensitive opiate site, and a naloxone-insensitive site which might involve catecholaminergic mediation similar to the PCP mechanism of action. The naloxone-sensitive effects of cyclazocine, however, may be related to an interaction of the drug with kappa receptors rather than with the more classical mu or delta opiate mechanisms.