650 J.A. Ramos et al.
in females they are frequently smaller and transient, as has also been reported for
other drugs of abuse (Fernández-Ruiz et al. 1992).
3.2
γ-Aminobutyric Acid
Cannabinoid receptors are frequently located on GABA-releasing neurons, for ex-
ample in the basal ganglia and the hippocampus (Herkenham et al. 1991), or on
non-GABAergic neurons that connect with GABA-releasing neurons, for example
in the cerebellum, where cannabinoid and GABA receptors colocalize in the same
neurons (Pacheco et al. 1993). Perinatal cannabinoid exposure has been found
not to produce any measurable change in GABA content or in the activity of
glutamic acid decarboxylase (GAD) in motor (caudate-putamen, globus pallidus,
and substantia nigra) and limbic (nucleus accumbens and ventral-tegmental area)
regions of adult animals. However, both adult male and females that had been
perinatally exposed to∆^9 -THC exhibited a higher responsiveness to the GABAB
receptor agonist, baclofen (García-Gil et al. 1999b). This is in concordance with
the predominant role proposed for GABABreceptors in the relationships between
GABA and endocannabinoids in the basal ganglia (Romero et al. 1996) and in other
brain regions in adult individuals. The changes in the motor responsiveness to ba-
clofen mimicked those observed previously with dopaminergic antagonist, which
supports the possibility that the effects on dopaminergic activity are mediated
through GABAergic neurons (García-Gil et al. 1996).
3.3
Serotonin
In brain development, 5-HT, like DA, exerts a trophic action, by a reciprocal in-
teraction with other neurotransmitters, in specific development processes (Pares-
Herbute et al. 1989). Some studies have reported changes in 5-HT development in
rats perinatally exposed to∆^9 -THC. Thus, this cannabinoid produced a decrease in
5-HT content in diencephalic areas but not in other brain areas (Molina-Holgado
et al. 1996). When animals perinatally exposed to∆^9 -THC matured, they exhibited
an increased 5-HT activity/metabolism in the hypothalamus, neostriatum, hip-
pocampus, septum nuclei, and midbrain raphe nuclei. Some of these effects were
only seen in males, indicating a sexually dimorphic response (Molina-Holgado et
al. 1997).
3.4
Opioid Peptides
Perinatal exposure to cannabinoids can also alter the development of opioidergic
neurons. It has been reported that the administration of cannabinoids increases