Acute effects of delta-9-tetrahydrocannabinol on dopaminergic activity in several rat brain areas.
In this work, we examined the acute effects of two doses of delta-9-tetrahydrocannabinol (THC) on several pre- and postsynaptic biochemical measures of dopaminergic activity in the striatum, limbic forebrain, and hypothalamic-anterior pituitary area of adult male rats. The exposure to a low dose of THC (0.5 mg/kg bw) decreased the number of striatal D2 dopaminergic binding sites, but did not affect their affinity. Treatment with a higher dose of THC was ineffective. In addition, both doses decreased the number of D1 dopaminergic binding sites in the limbic forebrain without changing their affinity. We did not find any changes in the dopamine (DA) or L-3,4-dihydroxyphenylacetic acid (DOPAC) content, or in the DOPAC/DA ratio, in either the striatum or limbic forebrain. THC treatment produced a dose-related decline in plasma prolactin (PRL) levels. Furthermore, both the basal and DA-inhibited in vitro release of PRL were reduced in animals exposed to THC in a dose-dependent manner. This inhibitory effect of THC on PRL release was accompanied by a decreased DOPAC/DA ratio in medial basal hypothalamus that, in turn, may be a result of the fall in PRL levels rather than a direct action of the drug. These data show that acute exposure to THC can alter brain dopaminergic neurotransmission. Our results suggest that the reduction of PRL release following THC exposure, both in vivo and in vitro, might be elicited by a direct action of THC on the pituitary.
Rodríguez De Fonseca
F
F
Department of Biochemistry, Faculty of Medicine, Complutense University, Madrid, Spain.
Fernández-Ruiz
J J
JJ
Murphy
L L
LL
Cebeira
M
M
Steger
R W
RW
Bartke
A
A
Ramos
J A
JA
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000378:metabolism / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008032:Limbic System / Q000187:drug effects; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013569:Synapses / Q000187:drug effects
D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D015102:3,4-Dihydroxyphenylacetic Acid; D013759:Dronabinol; D011388:Prolactin; D004298:Dopamine