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Experimental evidence suggests an important role of serotonin in the process of learning and memory. The present study investigated the effect of 5HT3-receptor antagonist (ICS 205-930) on retrieval of a previously learned aversive habit in the mouse. The effect of ICS 205-930 on scopolamine (3 mg/kg) induced amnesia was also studied. ICS 205-930 (1, 10 & 100 micrograms/kg) produced a dose-dependent increase in latency to cross into the dark chamber. The scopolamine induced memory impairment was significantly attenuated by ICS 205-930 (10 micrograms/kg). These results suggest that memory deficits may be susceptible to attenuation with non-cholinergic treatments.

The pharmacokinetics of progesterone (dose: 10 jig per animal) were studied in blood and cerebrospinal fluid of adult ovariectomized rhesus monkeys after the administration of the steroid as an intravenous injection, intravenous infusion (duration of infusion: 10 min), or nasal spray. The bioavailability of progesterone, in terms of area under the time-concentration curve and the maximal concentration in the two body fluids, was significantly higher when the steroid was infused or sprayed intranasally than when it was injected intravenously. The clearance of the steroid from the serum, as estimated by its elimination rate constant, elimination half-life, and total body clearance, did not differ for the three methods ofadministration. These findings suggest that the bioavailability of progesterone is enhanced by extending the duration over which the steroid is delivered into the hemal circulation.Reports from our laboratories have shown that marked neuroendocrine effects leading to an impairment of ovarian (1) or testicular (2) functions occur after the intranasal spraying ofprogesterone in extremely low doses likely to be ineffective when administered by oral or systemic routes. It has been suggested (3) that these marked effects observed with low doses of the steroid administered by an unconventional route may be related to the rapid and preferential transfer of the steroid to the brain via the cerebrospinal fluid (CSF). This suggestion is based on the finding of much higher levels of progesterone in the CSF after its being sprayed intranasally in comparison with its systemic administration (4,5).Because the pharmacological effects of a drug are known to be related to its bioavailability to target tissues rather than to its administered dose, it was felt that a comparison of the pharmacokinetics of progesterone after its systemic administration and intranasal spraying would be useful in furthering our understanding of these unique, low-dose effects occurring upon administering the steroid by an unconventional method. The studies reported here were carried out to obtain such data with particular reference to the bioavailability ofprogesterone to tissues bathed by blood, CSF, or both after the administration of progesterone by three different methods: intravenous (i.v.) injection, i.v. infusion, and nasal spray (n.s.).MATERIALS AND METHODS Animals. Six healthy adult female rhesus monkeys of similar body weights (5-6.5 kg) and sizes (6) were selected from the Primate Research Facility of our institute (7). These animals consistently exhibited ovulatory menstrual cycles ofnormal duration (23-28 days) before they were ovariectomized. They were used 2 months after ovariectomy. The clinical condition of all the animals, with particular reference to their liver and renal functions, as evaluated by estimating blood or serum levels of proteins, albumin, bilirubin, alkaline phosphatase, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, urea, and creatinine were within normal values reported for th...

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