Pregnancy outcome following gestational exposure to echinacea: a prospective controlled study.

BACKGROUND: Echinacea products are among the most popular phytomedicines on the North American market. Since at least half of all pregnancies are unplanned, many women inadvertently use echinacea in their first trimester. Presently, there is a paucity of information regarding the gestational safety of this herb. The primary objective of this study was to evaluate the safety of echinacea in pregnancy when used for upper respiratory tract ailments. PATIENTS AND METHODS: The study group consisted of women who were prospectively followed up after contacting the Motherisk Program regarding the gestational use of echinacea. This cohort was disease-matched to women exposed to nonteratogenic agents by maternal age, alcohol, and cigarette use. Rates of major and minor malformations between the groups were compared. RESULTS: A total of 206 women were enrolled in the study group after using echinacea products during pregnancy; 112 women used the herb in the first trimester. There were a total of 195 live births, including 3 sets of twins, 13 spontaneous abortions, and 1 therapeutic abortion. Six major malformations were reported, including 1 chromosomal abnormality, and 4 of these malformations occurred with echinacea exposure in the first trimester. In the control group, there were 206 women with 198 live births, 7 spontaneous abortions, and 1 therapeutic abortion. Seven major malformations were reported. There were no statistical differences between the study and control groups for any of the end points analyzed. CONCLUSIONS: This first prospective study suggests that gestational use of echinacea during organogenesis is not associated with an increased risk for major malformations.

Separate neural substrates mediate the motivating and discriminative properties of morphine.

A previous study (T. V. Jaeger & D. van der Kooy, 1993) has implicated a visceral and taste region (parabrachial nucleus), but not mesolimbic dopamine terminal fields (nucleus accumbens), as a substrate for opiate discriminative effects. The authors now show that (a) morphine's discriminative effects in the parabrachial nucleus (PBN) require the activation of opiate receptors; (b) in rats trained to discriminate morphine from saline, infusions of morphine into the ventral tegmental area (VTA) do not generalize to the systemic training condition; (c) infusions of morphine into the PBN, but not the VTA, serve as a stimulus for the acquisition of discrimination learning; and (d) morphine applied to the VTA, but not the PBN, is motivating. The data show that the motivating and discriminative effects of morphine are processed separately by the brain. Further, discriminative drug effects are neither necessary nor sufficient for opiate motivational effects.

Morphine acts in the parabrachial nucleus, a pontine viscerosensory relay, to produce discriminative stimulus effects.

Morphine is known to act centrally to produce discriminative stimulus effects, but the specific neuroanatomical sites mediating this action have not been identified. We used morphine as a discriminative stimulus in a taste aversion paradigm to elucidate the neural basis of morphine's cueing properties. Rats were injected subcutaneously with 5 mg/kg morphine 15 min prior to the presentation of a 0.1% saccharin solution. After 20 min of exposure to the flavor, lithium chloride (130 mg/kg, IP) was injected. On alternate days, an injection of 0.9% physiological saline both preceded and followed the presentation of saccharin. Animals learned to consume significantly less saccharin after morphine than after saline injections. Unilateral guide cannulae were then implanted into brain areas containing relatively high densities of opiate binding sites, comprising the medial prefrontal cortex, the nucleus accumbens, the anterior dorsolateral striatum, the medial thalamus, the basolateral amygdaloid nucleus, the dorsal hippocampus, the caudal periaqueductal grey and the parabrachial nucleus. Generalization to central routes of administration was then evaluated by microinjecting morphine (2.5, 5, 10 and 20 micrograms) into these brain areas. Dose-dependent decreases in saccharin consumption similar to those of systemic morphine were produced by the administration of morphine into the parabrachial nucleus and the nucleus accumbens. Control data showed that only in the parabrachial nucleus could these effects be attributed to the cueing properties of morphine; in the nucleus accumbens, morphine administration induced unconditioned decreases in saccharin consumption. In the remaining brain areas, morphine generalized to the systemic saline condition.(ABSTRACT TRUNCATED AT 250 WORDS)

A taste aversion model of drug discrimination learning: training drug and condition influence rate of learning, sensitivity and drug specificity.

A model of drug discrimination based on a lithium chloride (LiCl) flavour aversion was described and examined. Mildly thirsty rats were presented daily with 4 ml of a distinctly flavoured solution which was followed on 50% of the days by an IP injection of LiCl. Prior to the flavour presentation, the rats were injection SC with saline or a training drug (0.04 mg/kg fentanyl or 20 mg/kg pentobarbital) to signal whether LiCl would follow. Almost all rats eventually exhibited stable behaviour that involved drinking most or all of the fluid when it was not to be followed by LiCl and little or no drinking when it was. Such discrimination occurred regardless of whether drug predicted LiCl (learned-discomfort) or predicted no LiCl (learned-safety). However, with fentanyl there were clear differences between rats trained with drug under learned-safety and under learned-discomfort conditions for 1) the rate of acquisition of stable performance as a function of LiCl dose, 2) generalization of the training dose to a test dose that was lower, and 3) elicitation of fentanyl responses by pentobarbital. These findings, together with indications that such effects did not always occur with pentobarbital as the training drug, were discussed from theoretical and practical perspectives.