Inhibitory effect of GABAergic drugs in cocaine-induced genital reflexes in paradoxical sleep-deprived male rats.

The aim of this study was to seek whether GABAergic drugs were involved in the action of cocaine on spontaneous genital reflexes (penile erection-PE, and ejaculation-EJ) of paradoxical sleep-deprived (PSD) male rats. After a 4-day period of PSD, each group was administered with GABAergic drugs 1 h prior to cocaine and placed in observation cages. The administration of gamma-aminobutyric acid (GABA)-A agonist (muscimol, 2 and 3 mg/kg sc) reduced the number of animals displaying PE, whereas all doses tested of muscimol and bicuculline significantly reduced the frequency of PE. Pretreatment with the lower doses of GABA-B antagonist, phaclofen (1 and 2 mg/kg sc), also significantly reduced the percentage of rats showing PE; however, after the higher dose injection, the proportion of animals with PE was similar to those seen after vehicle pretreatment. Both GABA-B agonist and antagonist significantly reduced the PE frequency for all doses used compared with the vehicle group. There were no significant differences between control and GABA-A drugs in EJ behavior, whereas phaclofen 2 mg/kg pretreatment increased the ejaculatory latency. These data show that GABAergic compounds inhibited PE in male PSD rats suggesting that this inhibition points to a differential role of GABA receptor subtypes.

Cocaine constricts immature cerebral arterioles by a local anesthetic mechanism.

The effect of cocaine on cerebral arterioles was determined in newborn pigs and the mechanism of action was examined in terms of its local anesthetic and sympathomimetic properties. Forty-three newborn piglets were anesthetized, equipped with a closed cranial window, and the diameter of pial arterioles was measured by intravital microscopy. Increasing concentrations of cocaine (10(-7) M to 10(-3) M) applied onto the cortical surface resulted in a dose-dependent decrease in arteriolar diameter. Coadministration with phentolamine, an alpha-adrenoceptor antagonist, did not inhibit the contractile response to cocaine even though phentolamine blocked the constriction to topically applied norepinephrine. In contrast, coadministration of either tetrodotoxin (Na+ channel blocker), charybdotoxin (K+ channel blocker), or quinacrine (phospholipase A2 inhibitor), or pretreatment with indomethacin (cyclooxygenase inhibitor) attenuated vasoconstriction induced by cocaine. Topically applied lidocaine (10(-7) M to 10(-3) M), a local anesthetic without sympathomimetic properties, caused a dose-dependent constriction similar to cocaine, whereas topically applied nomifensine and desipramine (each 10(-7) M to 10(-3) M), inhibitors of dopamine and norepinephrine re-uptake, respectively, did not constrict cerebral arterioles. These results indicate that cocaine constricts cerebral arterioles by its local anesthetic properties rather than its sympathomimetic properties. The mechanism appears to involve an alteration in the flux of Na+ or K+ or prostanoid metabolism.