Gender differences in the behavioral responses to cocaine and amphetamine. Implications for mechanisms mediating gender differences in drug abuse.

When ovariectomized female rats receive estrogen, the response to the psychomotor stimulants amphetamine or cocaine is enhanced. Estrous cycle-dependent differences in amphetamine-stimulated behaviors and striatal dopamine release are also noted. Intact female rats exhibit a greater behavioral response to amphetamine on estrus than they do on other days of the cycle. Ovariectomy results in attenuation of amphetamine-induced behavior and the striatal dopamine response to amphetamine. Physiological doses of estrogen given to ovariectomized rats reinstate both of these responses to a level comparable to that in estrous females. Furthermore, a sex difference is noted, in that females tend to exhibit a greater behavioral response to the psychomotor stimulants, and estrogen enhances this sex difference. Repeated treatment with amphetamine or cocaine produces a progressive increase in behavioral responsiveness with subsequent drug administration, a process known as sensitization. In rodents, behavioral sensitization results in increases in both frequency and duration of psychomotor behaviors such as rotational behavior, stereotyped grooming, headbobs, and forelimb movements. Interestingly, females display greater sensitization of behaviors in response to psychomotor stimulants than do males. Previous research results are summarized, and new results are presented, demonstrating that estrogen selectively enhances components of behavior that exhibit sensitization in female rats. Results also indicate gender differences in sensitization independent of gonadal hormones, suggesting that the neural systems that undergo sensitization are sexually dimorphic.

[Azoles. 17. Beta-(4-pyrazol)acrylic and propionic acids and their anti-inflammatory activity]. / Azole. 17. Mitteilung1: Beta-(4-Pyrazol)acryl- bzw. -propionsäure und ihre antiphlogistische Wirkung.

beta-(4-Pyrazole)acrylic acids 22-28 were prepared by the Knoevenagel reaction of malonic acid and 4-formylpyrazoles 8-14. 4-Pyrazolemethylenemalonic acids 15-21 were isolated as intermediates. The latter compounds were also synthesized by treating the 4-formylpyrazoles 8-14 with diethyl malonate followed by hydrolysis of the obtained diethyl esters 15a-21a. The effect of piperidine and pyridine on the Knoevenagel condensation was investigated. The beta-(4-pyrazole)acrylic acids 22-27, on catalytic reduction, gave the corresponding beta-(4-pyrazole)propionic acids 29-34. Compounds 23, 24, 27, 29-31 and 34 appeared to be less active than phenylbutazone in carrageenin-induced oedema test, but they were less toxic than the reference drug.