Cannabinoid receptor antagonism increases female sexual motivation

López, Hassan H.; Webb, Sarah; Nash, Sean

doi:10.1016/j.pbb.2008.10.004

Cited by 27 publications

(23 citation statements)

References 57 publications

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“…For example, Δ 9 -tetrahydrocannabinol decreases gonadotropin secretion, thereby depressing ovarian steroidogenesis and disrupting ovarian cyclicity and pregnancy (Asch et al, 1981;Asch and Smith, 1986). Endogenous cannabinoids have also recently been shown to tonically inhibit sexual behavior in steroid-primed female rats (López et al, 2009). By contrast, cannabinoid CB 1 receptor agonists stimulate appetite in mice (Sinnayah et al, 2008), rats (Williams and Kirkham, 2002) and guinea pigs (Ho et al, 2007;Diaz et al, 2009), and in humans dronabinol and marijuana have been utilized as pharmacotherapeutic adjuncts to ameliorate body wasting in cancer (Walsh et al, 2005) and HIV/AIDS (Woolridge et al, 2005;Haney et al, 2005) patients.…”

Section: Introductionmentioning

confidence: 99%

Estrogen rapidly attenuates cannabinoid-induced changes in energy homeostasis

Kellert

Nguyen

et al. 2009

European Journal of Pharmacology

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We examined whether estrogen negatively modulates cannabinoid-induced regulation of food intake, core body temperature and neurotransmission at proopiomelanocortin (POMC) synapses. Food intake was evaluated in ovariectomized female guinea pigs abdominally implanted with thermal DataLoggers and treated s.c. with the cannabinoid CB 1 /CB 2 receptor agonist WIN 55,212-2, the CB 1 receptor antagonist AM251 or their cremephor/ethanol/0.9% saline vehicle, and with estradiol benzoate (EB) or its sesame oil vehicle. Whole-cell patch clamp recordings were performed in slices through the arcuate nucleus. WIN 55,212-2 produced dose-and time-dependent increases in food intake. EB decreased food intake 8-24 h after administration, but rapidly and completely blocked the increase in consumption caused by WIN 55,212-2. EB also attenuated the WIN 55,212-2-induced decrease in core body temperature. The AM251-induced decrease in food intake was unaffected. The diminution of the WIN 55,212-2-induced increase in food intake caused by EB correlated with a marked attenuation of cannabinoid receptor-mediated decreases in glutamatergic miniature excitatory postsynaptic current frequency occurring within 10-15 minutes of steroid application. Furthermore, EB completely blocked the depolarizing shift in the inactivation curve for the A-type K + current caused by WIN 55,212-2. The EB-mediated, physiologic antagonism of these presynaptic and postsynaptic actions elicited upon cannabinoid receptor activation was observed in arcuate neurons immunopositive for phenotypic markers of POMC neurons. These data reveal that estrogens negatively modulate cannabinoid-induced changes in appetite, body temperature and POMC neuronal activity. They also impart insight into the neuroanatomical substrates and effector systems upon which these counter-regulatory factors converge in the control of energy homeostasis.

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Section: Introductionmentioning

confidence: 99%

Estrogen rapidly attenuates cannabinoid-induced changes in energy homeostasis

Kellert

Nguyen

et al. 2009

European Journal of Pharmacology

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“…As such, there was less inherent reliability in our estrous data, making comparisons between nonestrous and estrous more difficult. Secondly, we have noted in previous publications (López et al, 2007, 2009) that RT, as a dependent variable, tends to demonstrate greater within-group variance when compared to PT. Perhaps this is because RT can be easily influenced by disruptive stimuli that occur at the start of a runway trial or transient emotional states, such as disorientation.…”

Section: Discussionmentioning

confidence: 70%

“…This apparatus has been previously utilized to assess socio-sexual motivation in both male (López and Ettenberg, 2000, 2001, 2002; López et al, 1999) and female rats (López et al, 2007, 2009, 2010; Nofrey et al, 2008). …”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, acute administration of cannabinoid agonists and antagonists has been shown to significantly affect the expression of both male and female sexual behavior (Gorzalka et al, 2010). Our laboratory has found that acute administration of the CB 1 R antagonist/inverse agonist, AM251, increased incentive sexual motivation in estrous female rats (López et al, 2009), and acute administration of the CB 1 R agonist, CP-55,940, dose-dependently attenuated sexual motivation in estrous females (López et al, 2010). These observations have led us to hypothesize that the eCB system helps regulate the expression of female sexual motivation across the ovarian cycle.…”

Section: Introductionmentioning

confidence: 99%

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

Chadwick

Saylor

López

2011

Pharmacology Biochemistry and Behavior

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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 CB1R 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. CB1R 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 CB1R expression in the ventromedial nucleus of the hypothalamus and amygdala. Drug treatment did not affect CB1R 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.

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“…Sexual behaviors are affected by drugs of abuse in humans and in rodents (Holder et al, 2009; Lopez et al, 2009; Pallonen et al, 2008). Under non-manipulated circumstances, male and female proestrous rats are expected to have high sexual behaviors, whereas female diestrous rats are expected to have low sexual behaviors (Beyer et al, 2007; Blaustein, 2008; Pfaus et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Low doses of cocaine decrease, and high doses increase, anxiety-like behavior and brain progestogen levels among intact rats

Kohtz

Paris

Frye

2010

Hormones and Behavior

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There are sex and hormonal differences in response to cocaine that have been demonstrated in people and animal models. Cocaine can alter secretion of progestogens, such as progesterone (P), and its neuroactive metabolite, 5α-pregnan-3α-ol-20-one (3α,5α-THP). However, little research has been done on the neuroendocrine effects in the initiation phase of cocaine use. We hypothesize that some sex/hormonal differences in initiation phase responses to cocaine may be related to formation of progestogens. To investigate the role of progestogens in sex differences in response to acute cocaine, male and female rats in the high (proestrous) or low (diestrous) progestogen phase of the estrous cycle were administered cocaine (0, 5, 10, or 20 mg/kg, IP). We examined cocaine's acute neuroendocrine effects on P and 3α,5α-THP levels, as well as its effects on acute psychomotor stimulation, anxiety, and sexual behaviors. Among rats that had P and/or 3α,5α-THP levels increased in response to cocaine, enhanced acute psychomotor stimulation was observed. Results suggest that cocaine produces U-shaped curves for progestogens, and anxiety-like behaviors. Male rats were less susceptible to these effects of cocaine than were proestrous or diestrous female rats. However, cocaine's disruption of sexual behaviors was similar among males and proestrous females. These data suggest a complex interaction between hormonal milieu and the neuroendocrine and behavioral effects of cocaine.

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Cannabinoid receptor antagonism increases female sexual motivation

Cited by 27 publications

References 57 publications

Estrogen rapidly attenuates cannabinoid-induced changes in energy homeostasis

Estrogen rapidly attenuates cannabinoid-induced changes in energy homeostasis

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

Low doses of cocaine decrease, and high doses increase, anxiety-like behavior and brain progestogen levels among intact rats

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