The mammalian hippocampus is a chief neural region involved in cognition and memory formation, and a principal structure mediating the neuropsychiatric side effects of cannabinoid exposure. Despite evidence that cannabis use during pregnancy can precipi...

Marijuana (Cannabis sativa) is one of the most used illicit drugs in our society. Impairment in brain functions and behavioral problems have been documented in children exposed to marijuana during prenatal development. The active component of marijuana, D9-tetrahydrocannabinol acts through cannabinoid receptor in the brain which tightly interacts with the mesocorticolimbic dopamine and endogenous opioid system. We have previously identified reduced dopamine D2 receptor mRNA expression in amygdala of prenatal cannabis-exposed human fetuses. The present study investigated the effects of in utero cannabis exposure on D2 expression levels in nucleus accumbens (NAc) and opioid-related genes in the human fetal forebrain. The study group consisted of midgestational fetuses from saline-induced voluntary abortion. The effect of prenatal cannabis exposure was analyzed by multiple regression controlling for confounding variables (maternal alcohol and cigarette use, fetal age, sex, postmortem interval and fetal growth...

Introduction: Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disease commonly caused by 3R (Pick’s disease, “PiD”) or 4R tauopathies (corticobasal degeneration, “CBD” and progressive supranuclear palsy, “PSP”). FTLD-tauopathies can lead...

Interest in cannabis and cannabinoid research for treatment of neurological disorders have received growing attention over the past years. Although there is evidence from animal and human studies that cannabis has some symptomatic effects, many therapeu...

In the nervous system, Ca2+-dependent facilitation and inactivation (CDF and CDI) of Cav2.1 channels may fine-tune presynaptic Ca2+ concentrations and contribute to activity-dependent synaptic plasticity. The mechanism for this dual feedback regulation by Ca2+ may involve calmodulin (CaM) binding directly to two sites, a CaM-binding domain (CBD) and an IQ-like domain in the C-terminal portion of the Cav2.1 α1 subunit (α12.1). In this study, we describe the molecular determinants for Ca2+-dependent modulation of Cav2.1, which reside both in CaM itself and in the CBD and IQ-like domain of α12.1. In transfected tsA-201 cells, CDI but not CDF was largely reduced in channels lacking the CBD. By contrast, alanine substitution of the first two residues of the IQ-like domain (IQ-AA) prevented CDF but not CDI. Moreover, Cav2.1 channels lacking the CBD and containing the IQ-AA mutations were deficient in both CDI and CDF. Ca2+ binding to CaM was critical for CDI and CDF, which were both nearly abolished by inactivat...

The rewarding properties of the psychoactive constituents of marijuana, termed “cannabinoids,” may reflect actions on synaptic transmission in the nucleus accumbens (NAc). Furthermore, long-term changes in these synapses may support the addictive process. Excitatory and inhibitory synapses are acutely inhibited by cannabinoids in the NAc, and endogenous cannabinoids (endocannabinoids) play a critical role in the expression of long-term depression (LTD) of excitatory cortical afferents in this structure. Because humans often use marijuana for prolonged periods, we examined the impact of long-term cannabinoid exposure on synaptic processes in an animal model. Electrophysiological recordings in rat brain slices containing the NAc were performed after chronic exposure to vehicle solution, Δ9-tetrahydrocannabinol (THC), or the cannabinoid agonist R (+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-(1-naphthalenyl)methanone mesylate (WIN55,212-2). Extracellular glutamatergic...

Clinical and preclinical studies indicate prenatal cannabis exposure (PCE) pathologically effects fetal brain development and may increase vulnerability to neuropsychiatric disorders, including schizophrenia, cognitive and mood/anxiety disorders. Howeve...

Aggregated microtubule associated protein tau in neurofibrillary tangles is a pathological hallmark of Alzheimer’s disease (AD). In other tauopathies, such as corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP), astrocytic tau inclu...

Delta9(-)-tetrahydrocannabinol (THC) in marijuana as well as anandamide, an endogenous ligand for cannabinoid receptors, increases food intake and body weight (Cota et al., 2003a; Hao et al., 2000; Williams and Kirkham, 2002). Prior studies suggest that endogenous cannabinoids and their receptors are present in the lateral hypothalamic area (Cota et al., 2003b; Moldrich and Wenger, 2000). In addition, immunohistochemical and in situ hybridization studies demonstrated that leptin receptors are found within the LH (Elmquist et al., 1998; Hakansson et al., 1998). We examined the mechanism by which THC may stimulate appetite in studies of synaptic transmission within the LH. We examined endocannabinoid signaling and tested for effect of leptin on endocannabinoid signaling by comparing synapses in wild-type (+/+) lateral hypothalamic slices with slices obtained from leptin deficient (ob/ob) mice. Brief depolarization of postsynaptic neurons depressed GABAergic transmission in all mice independent of genotype. L...

Several lines of evidence suggest direct actions of delta 9-tetrahydrocannabinol (THC), the main psychoactive constituent of Cannabis sativa, in modulating brain noradrenergic neurons. Noradrenergic neurons have been shown to play an important role in the manifestation of catalepsy induced by THC (Kataoka et al., Neuropharm. 26:55-60, 1987). In addition, cannabinoids activate descending noradrenergic neurons resulting in antinociception via the stimulation of spinal alpha 2-adrenoceptors (Lichtman and Martin, Brain Res. 559:309-314, 1991). Finally, exposure of pregnant rats to THC affects the gene expression and activity of tyrosine hydroxylase (TH) in the brains of their offspring (Bonnin et al., J Mol Neurosci, 7:291-308, 1996). In the present study, we examined the ultrastructural distribution of CB1 using immunoperoxidase or immunogold-silver labeling in the LC of adult male Sprague Dawley rats. Subsequently, we combined immunocytochemical detection of an antibody directed against the CB1 receptor and ...