Acute Effects of Δ^9-Tetrahydrocannabinol on Tuberoinfundibular Dopamine Activity, Anterior Pituitary Sensitivity to Dopamine and Prolactin Release Vary as a Function of Estrous Cycle

Abstract

The effects of Δ⁹-tetrahydrocannabinol (THC) on the activity of brain dopaminergic neurons might be subject to gonadal influence. In this work, we tested this hypothesis in relation to the effects of THC on tuberoinfundibular dopaminergic (TIDA) activity, the anterior pituitary sensitivity to dopamine (DA) and prolactin (PRL) secretion. To this end, we examined the effects of an acute dose of this cannabinoid administered during different phases of the estrous cycle in the morning or afternoon. The results were as follows. THC, administered during the morning of estrus, stimulated TIDA activity as reflected by increases in DA and L-3,4-dihydroxyphenylacetic acid (DOPAC) contents and tyrosine hydroxylase (TH) activity in the medial basal hypothalamus. This was accompanied by an increase in the responsiveness of the anterior pituitary to DA, as reflected by the increase in the density of D2 receptors and the corresponding decrease in PRL release. By contrast, plasma PRL levels increased when THC was administered on the afternoon of estrus, in parallel with a significant reduction in the number of D2 receptors in the anterior pituitary gland and no effects on TIDA activity. A similar decrease in the anterior pituitary density of D₂ receptors, but with no changes in plasma PRL levels, was observed when THC was administered during the morning of diestrus. This effect was not accompanied by changes in TIDA activity either. The administration of THC during the aftenoon of diestrus stimulated TIDA activity (increases in DA and DOPAC contents and TH activity in the medial basal hypothalamus), as occurred when the cannabinoid was administered during the morning of estrus, but in this case, it decreased the density of D2 receptors in the anterior pituitary and did not modify plasma PRL levels. These results contrast with the absence of significant changes observed when THC was administered during the morning or the afternoon of proestrus, although the highest plasma PRL levels and TIDA activity were observed during the afternoon of this phase. In summary, the effects of THC on TIDA activity, the sensitivity of the anterior pituitary to DA and PRL release seem to be under gonadal influence. This can be concluded from the observations that THC treatment caused different effects when administered to rats at different stages of the ovarian cycle. The classical inhibitory effect of THC on PRL release via an enhancement of TIDA activity observed in males was observed in females only during the morning of estrus. Different effects were seen during the diestrus and the afternoon of estrus, whereas its administration during proestrus was ineffective.

Long-Term Effects of Prenatal Exposure to Undernutrition on Cannabinoid Receptor-Related Behaviors: Sex and Tissue-Specific Alterations in the mRNA Expression of Cannabinoid Receptors and Lipid Metabolic Regulators

“…This limitation has to be considered in the interpretation of the data and further research will be addressed to evaluate the reasons for the sex-dimorphic alterations. However, it is important to note that in the female rat, sex steroids regulate both the expression and function of the endogenous cannabinoid system, so a potential explanation will also involve the impact of malnutrition on this important modulatory system, as it was described previously (Bonnin et al, 1993; Rodríguez de Fonseca et al, 1994). …”

Identification of Endocannabinoids and Cannabinoid CB₁ Receptor mRNA in the Pituitary Gland

“…Previous studies have reported that cannabinoid administration altered the activity of serotoninergic [18]and mainly dopaminergic [3, 7, 9, 18, 19, 20, 21, 22]neurons. These neurotransmitters are both involved, either directly or indirectly, in the control of neuroendocrine processes in the medial basal hypothalamus, in particular with regard to the control of PRL secretion.…”

Differential Effects of Chronic Treatment with Either Dopamine D₁ or D₂ Receptor Agonists on the Acute Neuroendocrine Actions of the Highly Potent Synthetic Cannabinoid HU-210 in Male Rats

“…To this end, we have studied the effects of chronic treatment with either DA D| (SKF 38393) or Di (quinpirole) receptor ag onists on the acute neuroendocrine actions of a low dose (20 jag/kg) of HU-210. This low dose is very close to the ED50 observed for producing the classically described cannabinoid-induced neurobehavioral effects such as cat alepsy, immobility or analgesia [ 17,22,29], The study has been carried out using male Wistar rats, since we have recently described a possible modulation by sex steroids (estradiol and progesterone) of both hypothalamic canna binoid receptor density [30] and neuroendocrine effects of THC in both normal cycling and ovariectomized female rats [31]. We have analyzed: (a) plasma PRL, luteinizing hormone (LH), ACTH and corticosterone levels, (b) pitu itary PRL and LH contents and (c) the medial basal hypo thalamus (MBH) contents of DA, L-3,4-dihydroxyphenylacetic acid (DOPAC, the main DA intraneuronal me tabolite) and noradrenaline (NA).…”

“…On the day of analysis, the MBH were dissected as previously described [31] and assayed for monoaminergic parameters. This area consisted of a tissue block 2.5 mm deep extending from just caudal to the optic chiasm to the rostral margin of the mammillary bodies, and lateral to the hypothalamic sulci.…”