Behavioral and neurochemical effects of Δ 9-tetrahydrocannabinol in rats

Abstract

Effects of Δ 9-tetrahydrocannabinol (Δ 9-THC) were studied on self-stimulation (SS) behavior in rats with electrodes implanted at either the posterior hypothalamus (PH) or area ventralis tegmentum (A10 area). Its effects were also studied on spontaneous motor activity (SMA), rectal temperature, barbiturate sleeping time, and neurotransmitter levels in discrete brain areas. Two patterns of Δ 9-THC effects were observed in these experiments. One type consisted of gradual depression persisting over a prolonged period. Hypothermia, potentiation of barbiturate-induced sleep and decrease in SS responding to nonaroused subjects, are examples. These effects may be due to a generalized central depression. The other type, a triphasic effect, is characterized by an initial depression followed by a stimulation and then again depression, and was observed in SS in aroused subjects and also in SMA. The effects of the psychomotor stimulants (such as amphetamine and cocaine) were antagonized during the initial depressant phase and unaffected or even potentiated during the subsequent stimulant phase. The neurochemical studies demonstrated an initial decrease of dopamine (DA) levels in the caudate nucleus and diencephalon-midbrain (DM) and an increase of serotonin (5-HT) in DM and pons-medulla (PM) followed by an increase of DA and a decrease of 5-HT levels, and then their return to near normal levels in respective brain areas. These changes in neurotransmitter levels appear to be correlated to the triphasic behavioral effects.