SEX, DRUGS & ROCK n ROLL THE PHARMACOLOGICAL REVOLUTION IN DRUGS WHICH ENHANCE (MALE) SEXUAL RESPONSE USED TO BE THOUGHT (up until last year) THAT IF ANYTHING, MALES WERE OVERSEXED But that was only up to 1998, when Pfizer marketed Viagra as a treatment for "male erectile dysfunction" Market went ballistic in months (no pun intended!) Sold over a billion dollars worth of Viagra last year + AT $10 per each little blue pill! WHY?? Seem to be two reasons: Freud was wrong (again)!! FEMALES don't have penis envy, MEN do! Males of all cultures and at all times have been obsessed with, and fretted about, their genitalia and sexual performance + basis of much patent medicine, folk medicine in many cultures Impotence appears to be much more common than once thought, at least in males over 50 True incidence concealed by shame, embarrassment AND lack of effective treatments VIAGRA JUST THE TIP OF THE ICEBERG FEMALE sexual dysfunction doubtlessly more common than male sexual dysfunction Usually called "frigidity", and accepted as just the way "good" girls (often) are, AND SHOULD BE And clearly, the closer we get to a true aphrodisiac, the greater the (male) demand Already Viagra is hitting the street, starting to be used by much younger men in the belief that it promotes the normal male sexual response SEX AND THE BRAIN: THE MALE SEXUAL RESPONSE ENDOCRINOLOGY - THE BIG "T" Organizing effects during development Most male sexual differentiation is mediated by testosterone Maintenance effects in adulthood A steady supply of T is also necessary to maintain: + Male sex drive or libido + Full erection Aging and T reduction Testosterone release slowly declines with increasing age As does libido and sexual activity BRAIN REGIONS AND NEUROTRANSMITTERS The amygdala: Medial amygdala is important in male sexual arousal + Is larger in males than in females Possibly links sensory stimuli, including odors, to sexual arousal Receives dopaminergic input from VTA Temporal lobe epilepsy usually involves the amygdala, and is accompanied by low libido The medial preoptic area (MPOA) Plays a critical role in the male sexual response At least in rats contains the sexually dimorphic nucleus, 5 times larger in male than in female rats Also modulated by dopaminergic input from the VTA Spinal mechanisms In most mammals, including humans, erection and ejaculation are possible after upper spinal cord is severed At least in rats, an area of the lower spinal cord + is sexually dimorphic and larger in males + is maintained by testosterone + Is responsible for spinal control of the male sexual response SEX AND THE BRAIN: THE FEMALE SEXUAL RESPONSE ENDOCRINOLOGY Estrogen and progesterone priming in animals In MOST mammalian females, estrus ("heat") is caused by ovarian release of estrogen, followed by release of progesterone In human females? SOME evidence for mildly increased sexual receptivity timed to estradiol peaks But receptivity clearly exists at all stages of the menstrual cycle Testosterone and female sexual receptivity The female ovaries make T, and the adrenals produce related androgens T is now believed to play an important role in female libido Menopause, endocrine changes and libido At menopause both T and estrogens drop As does libido Estrogen replacement is common but doesn't help (much); T replacement may BRAIN REGIONS AND NEUROTRANSMITTERS The Ventromedial Hypothalamus (VMH) In rats, intact, functional VMH is necessary for sexual receptivity VMH is enriched in estrogen and progesterone receptors + a key part of the system which produces sexual behavior after estrogen and progesterone priming Following hormonal priming, norepi in VMH appears to play an important role in supporting sexual behavior SEX AND THE BRAIN: THE ORGASM AND AFTER POST-ORGASMIC SEX DIFFERENCES: Males experience a prolonged refractory period Females are potentially multi-orgasmic Males are sedated Females tend to be aroused ORGASM AND THE ENDOCRINE SYSTEM In both sexes, orgasm releases both oxytocin and prolactin into the blood We're unsure why, the current story is that: Oxytocin is responsible for the post-coital "glow", + may be important for female libido Prolactin may trigger the male refractory period Orgasm and the mesolimbic dopamine system In both sexes, orgasm releases a flood of dopamine in the nucleus accumbens SEXUAL MACHINERY: THE MALE ERECTION ANATOMY, HYDRAULICS AND THE ERECTION Anatomy In cross-section, the penis is composed primarily of two columns of tissue, the twin Corpora Cavernosa Penis This tissue is interlaced with blood-filled sinuses, criss-crossed with smooth muscle fibers Relaxation of chronically tightened musculature Sexual arousal releases neurotransmitters which cause the musculature of the corpora cavernose to RELAX resulting in partial erection due to blood filling the sinuses Constriction of venous drainage filling of sinuses exerts pressure on venous drainage Creating a full erection NEURAL CONTROL OF THE ERECTION NO (nitric oxide) Basically, nitric oxide leads to the production of another chemical, cyclic GMP, which causes muscles in the spongy erectile tissue of the penis to relax and allows the penile sinuses to expand during sexual stimulation. Adrenergic mechanisms These are quite complex beta adrenergic receptors cooperate in increasing blood flow into sinuses Yet norepi, acting through alpha receptors, also plays a dominant role in termination of erection via a direct constrictor effect on musculature Prostaglandins are also involved in relaxation of smooth musculature SEXUAL MACHINERY: FEMALE GENITAL AROUSAL LUBRICATION VASODILATION Including partial clitoral erection via mechanisms very similar to those in male erection