Hassan H. López

Attractive men induce testosterone and cortisol release in women

Recently, Roney et al. (Roney, J.R., Lukaszewski, A.W., Simmons, Z.L., 2007. Rapid endocrine responses of young men to social interactions with young women. Horm. Behav. 52, 326-33; Roney, J.R., Mahler, S.V., Maestripieri, D., 2003. Behavioral and hormonal responses of men to brief interactions with women. Evol. Hum. Behav. 24, 365-375) demonstrated that men release testosterone and cortisol in response to brief social interactions with young women. The current experiment examined whether women show a similar endocrine response to physically and behaviorally attractive men. 120 women (70 naturally-cycling and 50 using hormonal contraceptives) were shown one of four 20-minute video montages extracted from popular films, depicting the following scenarios: 1) an attractive man courting a young woman (experimental stimulus), 2) a nature documentary (video clip control), 3) an unattractive older man courting a woman (male control), and 4) an attractive woman with no men present (female control). Saliva samples were taken before and after presentation of the stimulus, and were later analyzed for testosterone and cortisol content via enzyme immunoassay. Naturally-cycling women experienced a significant increase in both testosterone and cortisol in response to the experimental stimulus but to none of the control stimuli. Participants taking hormonal contraceptives also showed a significant cortisol response to the attractive man. Women may release adrenal steroid hormones to facilitate courtship interactions with high mate-value men.

Cannabinoid receptor antagonism increases female sexual motivation

The current experiments examined whether treatment with a CB1 antagonist/inverse agonist (AM251) affects sexual motivation, proceptivity, and receptivity in female rats. In experiment #1, 92 Long-Evans rats were tested for their socio-sexual motivation via a runway methodology. Motivation to approach and maintain close proximity to an empty goalbox, a female, and a male target was assessed following hormonal and drug treatment. Hormone treatments were: oil vehicle, 10 microg estradiol, and 10 microg estradiol+500 microg progesterone. Drug doses were 0, 2, and 4 mg/kg AM251 (IP, 60 min prior to testing). In experiment #2, 32 female subjects were tested for receptivity and proceptivity in a paced mating chamber. Subjects were given either a high (10 microg estradiol+500 microg progesterone) or low dose of hormones (2 microg estradiol+250 microg progesterone), and either vehicle or 2 mg/kg AM251. AM251 significantly increased sexual motivation for a male target in the runway in females primed with both estradiol and progesterone. AM251 also enhanced lordosis (in low hormone females) and increased hop-darts. These findings suggest that endocannabinoids tonically inhibit estrous behaviors. Cannabinoid antagonists could serve as new treatment option for women suffering from abnormally low libido.

Adolescent cannabinoid exposure attenuates adult female sexual motivation but does not alter adulthood CB1R expression or estrous cyclicity

Adolescence is a developmental period characterized by neuronal remodeling and the maturation of adult emotionality, reproductive behavior and social behavior. We examined whether chronic cannabinoid exposure in adolescent rats alters female sexual motivation, estrous cyclicity, sucrose preference, and CB(1)R expression in adulthood. Female rats were administered with the synthetic cannabinoid agonist, CP-55,940 (0.4 mg/kg, intraperitoneal), daily during adolescent development (PND 35-45). In a subset of subjects, socio-sexual motivation was investigated in adulthood (PND 75-86) using a runway apparatus. Estrous cyclicity was tracked in adulthood via vaginal cytology and a single-mount test. A two-bottle sucrose preference test was also conducted to determine whether predicted changes in socio-sexual motivation might be linked to alterations in hedonic processing. CB(1)R expression was examined in two separate subsets of subjects, one sacrificed following drug treatment (PND 46) and one before behavioral testing (PND 74). Drug treatment significantly decreased adult preference for a male conspecific (sexual motivation), as assessed by both Run Time and Proximity Time, but did not affect estrous cyclicity or sucrose preference. CP-55,940 treatment also induced immediate, but transient, decreases in CB(1)R expression in the ventromedial nucleus of the hypothalamus and amygdala. Drug treatment did not affect CB(1)R expression in the nucleus accumbens (core or shell) or globus pallidus at either time point. We suggest that the endocannabinoid system may play a role in the maturation of neuroendocrine axes and adult female reproductive behavior, and that chronic exposure to cannabinoids during adolescence disrupts these neurodevelopmental processes.

Acute cannabinoid administration attenuates female socio-sexual motivation.

Endocannabinoids may normally inhibit the generation and expression of female estrous behaviors. Previous work in our laboratory demonstrated that acute administration of a CB(1) receptor antagonist (AM251) increased sexual incentive motivation in estrous female rats. The current experiment examined the effect of CP55,940, a synthetic cannabinoid agonist, on sexual motivation. Seventy-two ovariectomized female Long-Evans rats were tested for their socio-sexual motivation via a runway methodology. Baseline motivation to approach and maintain close proximity to an empty goalbox, a female conspecific, and a male conspecific was assessed over six trials. Subjects were then grouped into nine experimental conditions and re-tested for their socio-sexual motivation after one of three possible hormonal treatments and three drug doses. Hormone treatments were: oil (nonestrous), 10 microg estradiol benzoate (partially estrous), and 10 microg estradiol+500 microg progesterone (fully estrous). Drug doses were: 0, 20, or 40 microg/kg CP55,940 (IP, 30 min prior to testing). As expected, hormonal priming with both estradiol and progesterone significantly increased sexual motivation in females that did not receive drug treatment. This occurred even though females were kept sexually-naïve throughout the experiment. CP55,940 dose-dependently attenuated sexual motivation for a male target in estrous females; the 40 microg/kg dose completely blocked sexual motivation. However, this same dose also significantly reduced social motivation for another female. Cannabinoid agonists reduce female sexual motivation, either directly by inhibiting estrus or indirectly by increasing social anxiety.

Assessing the role of serotonergic receptors in cannabidiol's anticonvulsant efficacy

Cannabidiol (CBD) is a phytocannabinoid that has demonstrated anticonvulsant efficacy in several animal models of seizure. The current experiment validated CBDs anticonvulsant effect using the acute pentylenetetrazol (PTZ) model. Furthermore, it tested whether CBD reduces seizure activity by interacting with either the serotonergic 5HT1A or 5HT2A receptor. 120 male adolescent Wistar-Kyoto rats were randomly assigned to 8 treatment groups in two consecutive experiments. In both experiments, subjects received either CBD (100mg/kg) or vehicle 60min prior to seizure testing. In Experiment 1, subjects received either WAY-100635 (1mg/kg), a 5HT1A antagonist, or saline vehicle injection 80min prior to seizure testing. In Experiment 2, subjects received either MDL-100907 (0.3mg/kg), a specific 5HT2A antagonist, or 40% DMSO vehicle 80min prior to seizure testing. 85mg/kg of PTZ was administered to induce seizure, and behavior was recorded for 30min. Seizure behaviors were subsequently coded using a 5-point scale of severity. Across both experiments, subjects in the vehicle control groups exhibited high levels of seizure activity and mortality. In both experiments, CBD treatment significantly attenuated seizure activity. Pre-treatment with either WAY-100635 or MDL-100907 did not block CBDs anticonvulsant effect. WAY-100635 administration, by itself, also led to a significant attenuation of seizure activity. These results do not support the hypothesis that CBD attenuates seizure activity through activation of the 5HT1A or 5HT2A receptor. While this work further confirms the anticonvulsant efficacy of CBD and supports its application in the treatment of human seizure disorders, additional research on CBDs mechanism of action must be conducted.

The effects of adolescent cannabinoid exposure on seizure susceptibility and lethality in adult male rats.

There is substantial evidence in rodent models that chronic exposure to cannabinoids during adolescence can alter the development of neurobiological systems that are implicated in regulating brain activity and seizure. The current study explored whether adolescent cannabinoid treatment affects subsequent, adult seizure susceptibility. Sixty male Wistar Kyoto rats were treated with either the synthetic cannabinoid, CP 55,940 (0.4mg/kg, one treatment per day), or vehicle between 35 and 45days old. Subjects were then allowed to mature to adulthood. At 68-69days of age, subjects were tested for seizure susceptibility using the pro-convulsant, pentylenetetrazol (PTZ). Subjects received an acute injection of either 35mg/kg or 50mg/kg PTZ immediately prior to a 30-min behavioral seizure test. PTZ doses were chosen to produce low-to-moderate levels of seizure activity in control subjects. There were no significant differences between treated and control subjects in: latency to first seizure, mean seizure severity, percentage who displayed any seizure activity, percentage who displayed clonic seizure, or percentage who displayed tonic-clonic seizure. However, CP 55,940-treated subjects had a higher mortality rate compared to controls at both PTZ doses, suggesting that adolescent cannabinoid exposure may increase the lethality of severe seizures experienced in adulthood.