An acute dose of delta 9-tetrahydrocannabinol affects behavioral and neurochemical indices of mesolimbic dopaminergic activity.
Cannabinoid consumption has been reported to affect several neurotransmitter systems and their related behaviors. The present study has been designed to examine cannabinoid effects on certain behaviors, which have been currently located in the limbic forebrain, in parallel to their effects on mesolimbic dopaminergic neurons. To this end, male rats treated with an oral dose of delta 9-tetrahydrocannabinol (THC) or vehicle were used 1 h after treatment for two different behavioral tests or neurochemical analyses of mesolimbic dopaminergic activity. Treatments, behavioral tests and sacrifice were performed in the dark phase of photoperiod because it corresponds to the maximum behavioral expression in the rat. Behavioral tests were a dark-light emergence test, which allows measurements of emotional reactivity, and a socio-sexual approach behavior test, which allows measurements of sexual motivation and also of spontaneous and stereotypic activities. Neurochemical analyses consisted of measurements of dopamine (DA) and L-3,4-dihydroxyphenylacetic acid (DOPAC) contents, tyrosine hydroxylase activity, in vitro DA release and number and affinity of D1 receptors in the limbic forebrain. Results were as follows. THC exposure markedly altered the pattern executed by the animals in both tests. Concretely, THC-exposed animals exhibited a low number of visits to an incentive female in addition to high time spent in the vicinity of an incentive male, both observed in the socio-sexual approach behavior test, and an increased emergence latency to go out of a dark compartment in the dark-light emergence test. However, the fact that THC also decreased spontaneous activity and the frequency of rearing and self-grooming behaviors, in addition to the observations of either low total number of visits to both incentive sexual areas or high escape latency to go out of a light compartment, when the animal is placed in this compartment, also suggest the possible existence of an accompanying motor deficit. These behavioral effects were accompanied by increases in DA and DOPAC contents and in D1 receptor density in the limbic forebrain and to a slight decrease in the pattern of K(+)-evoked DA release in vitro from perifused limbic fragments, with no changes in the remaining neurochemical parameters. Collectively, these results allow us to conclude that acute THC markedly altered the behavioral pattern executed by the animals in a socio-sexual approach behavior test and in a dark-light emergence test, presumably indicating loss of sexual motivation and increased emotionality, although also accompanied by motor deficiencies.(ABSTRACT TRUNCATED AT 400 WORDS)
Navarro
M
M
Department of Psychobiology, Faculty of Psychology, Complutense University, Madrid, Spain.
Fernández-Ruiz
J J
JJ
de Miguel
R
R
Hernández
M L
ML
Cebeira
M
M
Ramos
J A
JA
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001143:Arousal / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D013759:Dronabinol / Q000493:pharmacokinetics / Q000494:pharmacology*; D004644:Emotions / Q000187:drug effects; D008032:Limbic System / Q000187:drug effects*; D008297:Male; D008636:Mesencephalon / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects*; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D015102:3,4-Dihydroxyphenylacetic Acid; D013759:Dronabinol; D004298:Dopamine