Distribution of D5 Dopamine Receptor mRNA in Rat Ventromedial Hypothalamic Nucleus

Zhou, Dan; Apostolakis, Ede Marie; O’Malley, Bert W.

doi:10.1006/bbrc.1999.1851

Cited by 19 publications

(13 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar interactions could occur in the medial basal hypothalamic region of the brain, which contains a high density of CB 1 receptors and cell bodies or terminals of dopaminergic neurons (24,33). The expression of D 1 B in the PR-rich ventromedial nucleus of the rat brain also has been recently reported (46). The present data clearly indicate the involvement of dopamine D 1 B receptors in THC-facilitated receptivity, suggesting an interaction between the two pathways.…”

Section: Discussionsupporting

confidence: 84%

Progesterone receptor and dopamine receptors are required in Δ ⁹ -tetrahydrocannabinol modulation of sexual receptivity in female rats

Mani

Mitchell

O’Malley

2001

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Ovarian steroids, estrogen and progesterone, influence the sensitivity of certain neural processes to cannabinoid treatment by modulation of brain dopaminergic activity. We examined the effects of the active ingredient of cannabis, ⌬ 9 -tetrahydrocannabinol (THC), on sexual behavior in female rats and its influence on steroid hormone receptors and neurotransmitters in the facilitation of sexual receptivity. Our results revealed that the facilitatory effect of THC was inhibited by antagonists to both progesterone and dopamine D 1 receptors. To test further the idea that progesterone receptors (PR) and͞or dopamine receptors (D1R) in the hypothalamus are required for THCfacilitated sexual behavior in rodents, antisense and sense oligonucleotides to PR and D 1R were administered intracerebroventricularly (ICV) into the third cerebral ventricle of ovariectomized, estradiol benzoate-primed rats. Progesterone-and THC-facilitated sexual behavior was inhibited in animals treated with antisense oligonucleotides to PR or to D 1R. Antagonists to cannabinoid receptor-1 subtype (CB 1), but not to cannabinoid receptor-2 subtype (CB2) inhibited progesterone-and dopamine-facilitated sexual receptivity in female rats. Our studies indicate that THC acts on the CB 1 cannabinoid receptor to initiate a signal transduction response that requires both membrane dopamine and intracellular progesterone receptors for effective induction of sexual behavior.transcription factors ͉ cannabinoids ͉ signal transduction cross talk T he major psychoactive cannabinoid in marijuana, ⌬ 9 -tetrahydrocannabinol (THC), alters many reproductive parameters in both male and female laboratory animals and humans (1). In males, THC has been reported to reduce testosterone concentrations in the plasma (2, 3), suppress spermatogenesis, reduce the weight of testes and accessory reproductive organs (4), and decrease components of male sexual behavior (5-7). In the females, THC has been demonstrated to prolong estrous cycle of rats (8), decrease proestrous luteinizing hormone (LH) surge leading to inhibition of ovulation (9, 10), and stimulate sexual behavior (11,12). THCmediated effects on central dopaminergic systems lead to increased extracellular dopamine concentration (13). These effects on brain dopaminergic activity vary as a function of the gonadal status of the animal (14). Furthermore, ovarian sex steroid hormones also alter the density and affinity of cannabinoid (CB) receptors in steroidsensitive brain areas, suggesting that ovarian steroid hormones could alter the sensitivity of certain neuronal processes to THC treatment.Ovarian steroid hormones, estrogen (E) and progesterone (P), regulate cellular functions in the brain that control sexual behavior in the female rat (15, 16). Estrogen priming causes an increase in progesterone receptor (PR) levels in the hypothalamus and preoptic areas of the rat brain (17). We and others previously have demonstrated a critical role for hypothalamic PRs in the induction of sexual behavior by using PR antagonists and...

show abstract

Section: Discussionsupporting

confidence: 84%

Progesterone receptor and dopamine receptors are required in Δ ⁹ -tetrahydrocannabinol modulation of sexual receptivity in female rats

Mani

Mitchell

O’Malley

2001

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Nongenomic actions of estradiol have been proposed to involve several signal transduction pathways, dependent on cell type. McDonnell and colleagues have provided evidence for MAP kinase pathway components and intracellular calcium as important players (27), whereas the molecular pharmacological results of O'Malley and his coworkers make a strong case for dopamine and subsequent cAMP signaling in the CNS (28)(29)(30). Mitogenactivated protein kinase (MAPK) has been implicated in estrogen's rapid action at the membrane in the related cell line SK-N-SH (31), as have PKA (32) and PKC (33).…”

Section: Discussionmentioning

confidence: 99%

“…Dopamine agonists have been shown to activate ER in the SK-N-SH cell line, an effect blocked by PKA antagonists (39). The presence of D1 receptor in the ventromedial hypothalamus (VMH), a brain region rich in ER␣, and the ability of dopamine to induce lordosis (29) suggest that dopamine effects involving intracellular second messengers can activate ER and consequently result in an ER-controlled behavior.…”

Section: Discussionmentioning

confidence: 99%

Early membrane estrogenic effects required for full expression of slower genomic actions in a nerve cell line

Vasudevan

Kow

Pfaff

2001

Proc. Natl. Acad. Sci. U.S.A.

154

102

View full text Add to dashboard Cite

Interpretations of steroid hormone actions as slow, nuclear, transcriptional events have frequently been seen as competing against inferences of rapid membrane actions. We have discovered conditions where membrane-limited effects potentiate later transcriptional actions in a nerve cell line. Making use of a two-pulse hormonal schedule in a transfection system, early and brief administration of conjugated, membrane-limited estradiol was necessary but not sufficient for full transcriptional potency of the second estrogen pulse. Efficacy of the first pulse depended on intact signal transduction pathways. Surprisingly, the actions of both pulses were blocked by a classical estrogen receptor (ER) antagonist. Thus, two different modes of steroid hormone action can synergize.

show abstract

“…Using the time schedule for appearance of positive lordosis (60 min after P), brain tissue samples (n ϭ 3 animals per treatment group repeated thrice) were collected by micropunch technique using anatomical markers as described previously (31,56) at 44 h after EB sc (or sesame oil), and 1 h after P (icv). Tissue samples from all experiments were processed at the same time for RNA extraction and analysis.…”

Section: Rt-qpcr For Quantitative Analysismentioning

confidence: 99%

PAC1 Receptors Mediate Pituitary Adenylate Cyclase-Activating Polypeptide- and Progesterone-Facilitated Receptivity in Female Rats

Apostolakis

Riherd

O’Malley

2005

Molecular Endocrinology

Self Cite

View full text Add to dashboard Cite

Pituitary adenylate cyclase-activating polypeptide (PACAP) acts as a feed-forward, paracrine/autocrine factor in the hypothalamic ventromedial nucleus (VMN) for receptivity and sensitizes pituitary hormone release for ovulation. The present study examined receptor(s) and signaling pathway by which PACAP enhances rodent lordosis. PACAP binds to PACAP (PAC1)- and vasoactive intestinal peptide-preferring receptors (VPAC1, VPAC2). Ovariectomized rodents primed with estradiol (EB) were given PACAP or vasoactive intestinal peptide directly onto VMN cells. Only PACAP facilitated receptivity. Pretreatment with VPAC1 and VPAC2 inhibitors blocked both PACAP- and progesterone (P)-induced receptivity. Antisense (AS) oligonucleotides to PAC1 (not VPAC1 or VPAC2) inhibited the behavioral effect of PACAP and P. By real-time RT-PCR, EB, P and EB+P enhanced VMN mRNA expression of PAC1. Within the total PAC1 population, EB and EB+P induced expression of short form PAC1 and PAC1hop2 splice variants. Finally, blocking cAMP/protein kinase A signaling cascade by antagonists to cAMP activity and protein kinase A or by antisense to dopamine- and cAMP-regulated phosphoprotein of 32 kDa blocked the PACAP effect on behavior. Collectively, these findings provide evidence that progesterone receptor-dependent receptivity is, in part, dependent on PAC1 receptors for intracellular VMN signaling and delineate a novel, steroid-dependent mechanism for a feed-forward reinforcement of steroid receptor-dependent reproductive receptivity.

show abstract

Distribution of D5 Dopamine Receptor mRNA in Rat Ventromedial Hypothalamic Nucleus

Cited by 19 publications

References 23 publications

Progesterone receptor and dopamine receptors are required in Δ ⁹ -tetrahydrocannabinol modulation of sexual receptivity in female rats

Progesterone receptor and dopamine receptors are required in Δ ⁹ -tetrahydrocannabinol modulation of sexual receptivity in female rats

Early membrane estrogenic effects required for full expression of slower genomic actions in a nerve cell line

PAC1 Receptors Mediate Pituitary Adenylate Cyclase-Activating Polypeptide- and Progesterone-Facilitated Receptivity in Female Rats

Contact Info

Product

Resources

About

Distribution of D5 Dopamine Receptor mRNA in Rat Ventromedial Hypothalamic Nucleus

Cited by 19 publications

References 23 publications

Progesterone receptor and dopamine receptors are required in Δ 9 -tetrahydrocannabinol modulation of sexual receptivity in female rats

Progesterone receptor and dopamine receptors are required in Δ 9 -tetrahydrocannabinol modulation of sexual receptivity in female rats

Early membrane estrogenic effects required for full expression of slower genomic actions in a nerve cell line

PAC1 Receptors Mediate Pituitary Adenylate Cyclase-Activating Polypeptide- and Progesterone-Facilitated Receptivity in Female Rats

Contact Info

Product

Resources

About

Progesterone receptor and dopamine receptors are required in Δ ⁹ -tetrahydrocannabinol modulation of sexual receptivity in female rats

Progesterone receptor and dopamine receptors are required in Δ ⁹ -tetrahydrocannabinol modulation of sexual receptivity in female rats