PMID- 9825732
OWN - NLM
STAT- MEDLINE
DCOM- 19981207
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 56
IP  - 10
DP  - 1998 Nov 15
TI  - Effects of cannabinoids on prolactin and gonadotrophin secretion: involvement of 
      changes in hypothalamic gamma-aminobutyric acid (GABA) inputs.
PG  - 1331-8
AB  - CB1 cannabinoid receptors are located in hypothalamic nuclei and their activation 
      alters several hypothalamic neurotransmitters resulting in, among other things, 
      decreased prolactin (PRL) and luteinizing hormone (LH) secretion from the 
      anterior pituitary gland. In the present study, we addressed two related 
      objectives to further explore this complex regulation. First, we examined whether 
      changes in gamma-aminobutyric acid (GABA) and/or dopamine (DA) inputs in the 
      medial basal hypothalamus might occur in parallel to the effects resulting from 
      the activation of CB1 receptors on PRL and gonadotrophin secretion in male rats. 
      Thus, the acute administration of (-)-delta9-tetrahydrocannnabinol (delta9-THC) 
      produced, as expected, a marked decrease in plasma PRL and LH levels, with no 
      changes in follicle-stimulating hormone (FSH) levels. This was paralleled by an 
      increase in the contents of GABA, but not of DA, in the medial basal hypothalamus 
      and, to a lesser extent, in the anterior pituitary gland. The co-administration 
      of delta9-THC and SR141716, a specific antagonist for CB1 receptors, attenuated 
      both PRL and LH decrease and GABA increase, thus asserting the involvement of the 
      activation of CB1 receptors in these effects. As a second objective, we tested 
      whether the prolonged activation of these receptors might induce tolerance with 
      regard to the decrease in PRL and LH release, and whether this potential 
      tolerance might be related to changes in CB1-receptor binding and/or mRNA 
      expression. The chronic administration of R-methanandamide (AM356), a more stable 
      analog of anandamide, the putative endogenous cannabinoid ligand, produced a 
      marked decrease in plasma PRL and LH levels, with no changes in FSH. The 
      decreases were of similar magnitude to those caused by a single injection of this 
      cannabimimetic ligand, thus suggesting the absence of tolerance. In parallel, the 
      analysis of CB1-receptor binding and mRNA expression in several hypothalamic 
      structures proved that the acute or chronic administration of AM356 did not 
      affect either the binding or the synthesis of these receptors. In summary, the 
      activation of CB1 receptors in hypothalamic nuclei produced the expected decrease 
      in PRL and LH secretion, an effect which might be related to an increase in 
      GABAergic activity in the hypothalamus-anterior pituitary axis. The prolonged 
      activation of these receptors for five days did not elicit tolerance in terms of 
      an attenuation in the magnitude of the decrease in PRL and LH, and, accordingly, 
      did not alter CB1-receptor binding and mRNA levels in the hypothalamic nuclei 
      examined.
FAU - de Miguel, R
AU  - de Miguel R
AD  - Department of Biochemistry, Faculty of Medicine, Complutense University, Madrid, 
      Spain.
FAU - Romero, J
AU  - Romero J
FAU - Munoz, R M
AU  - Munoz RM
FAU - Garcia-Gil, L
AU  - Garcia-Gil L
FAU - Gonzalez, S
AU  - Gonzalez S
FAU - Villanua, M A
AU  - Villanua MA
FAU - Makriyannis, A
AU  - Makriyannis A
FAU - Ramos, J A
AU  - Ramos JA
FAU - Fernandez-Ruiz, J J
AU  - Fernandez-Ruiz JJ
LA  - eng
GR  - DA 3801/DA/NIDA NIH HHS/United States
GR  - DA 9158/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Arachidonic Acids)
RN  - 0 (Gonadotropins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cannabinoid)
RN  - 0 (Receptors, Drug)
RN  - 150314-39-9 (methanandamide)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 7J8897W37S (Dronabinol)
RN  - 9002-62-4 (Prolactin)
SB  - IM
MH  - Animals
MH  - Arachidonic Acids/pharmacology
MH  - Dronabinol/*pharmacology
MH  - Gonadotropins/*metabolism
MH  - Hypothalamus/*drug effects/metabolism
MH  - Male
MH  - Prolactin/*metabolism
MH  - Protein Binding
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Cannabinoid
MH  - Receptors, Drug/drug effects/genetics/metabolism
MH  - gamma-Aminobutyric Acid/*metabolism
EDAT- 1998/11/24 00:00
MHDA- 1998/11/24 00:01
CRDT- 1998/11/24 00:00
PHST- 1998/11/24 00:00 [pubmed]
PHST- 1998/11/24 00:01 [medline]
PHST- 1998/11/24 00:00 [entrez]
AID - S0006-2952(98)00185-3 [pii]
AID - 10.1016/s0006-2952(98)00185-3 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 1998 Nov 15;56(10):1331-8. doi: 10.1016/s0006-2952(98)00185-3.