Further evidence for cholinergic habenulo-interpeduncular neurons: pharmacologic and functional characteristics.

Placement of high frequency lesions in the medial habenular area results in a large depletion of acetylcholine (ACh) levels, choline acetyltransferase (ChAc) activity, and high affinity choline uptake in the interpeduncular nucleus area (IPN) at 1, 3 and 7 days post-lesion. Areas adjacent to the IPN did not have a reduction in ChAc activity. The reduction in high affinity choline uptake was selective in that there was no change in the uptake of L-[3H]tyrosine or L-[3H]glutamic acid. Unlike the cholinergic septal-hippocampal neurons, there was no rise in ACh levels in the IPN 1 h after placement of lesion, or 30 min after administration of pentobarbital. While the IPN probably has a much denser cholinergic innervation than the hippocampus (as evidenced by much higher ACh levels, ChAc activity and choline uptake levels), it has only one-fourth as many [3H]QNB binding sites (a measure of cholinergic muscarinic receptors). This, some of the habenulo-interpeduncular neurons are probably cholinergic, and they may have pharmacologic and functional differences compared to the septal-hippocampal neurons.     

Colocalization of CART with substance P but not enkephalin in the rat nucleus accumbens

CART peptide is a novel neurotransmitter that, due to its distribution in the brain and its modulation of dopamine systems, may be involved in aspects of reward and drug abuse. In the nucleus accumbens (NAcc), CART peptide immunoreactivity (IR) is colocalized with substance P-IR in neurons. Approximately 86% of CART-IR cells colocalize with substance P, while only 19% of substance P-IR neurons contain CART. CART peptide does not colocalize with enkephalin-IR in this region. The substance P-CART colocalization exists in a rostro-caudal gradient with more colocalization in rostral regions. The presence of CART in substance P NAcc neurons suggests that CART neurons may be a subset of the basal ganglia direct pathway or that CART neurons are involved in limbic projections of the NAcc, such as to the ventral pallidum.     

Synthesis, monoamine transporter binding properties, and behavioral pharmacology of a series of 3beta-(substituted phenyl)-2beta-(3'-substituted isoxazol-5-yl)tropanes

Several 3beta-(substituted phenyl)-2beta-(3-substituted isoxazol-5-yl)tropanes (3a-t) were evaluated for their ability to inhibit radioligand binding at the DAT, 5-HTT, and NET as well as in gross observation and locomotor activity in mice and in rats trained to discriminate cocaine. All compounds showed high affinity for the DAT. The IC(50) values ranged from 0.5 to 26 nM. With the exception of 3e and 3f, which have no substituent on the 2beta-(1,2-isoxazole) ring, all compounds were selective for the DAT relative to the 5-HTT and NET. No compound showed death when dosed at 100 mg/kg; however, most compounds did show signs typical of dopamine activity. The ED(50) values for 2beta-(1,2-isoxazoles) that caused locomotor stimulation ranged from 0.2 to 12.8 mg/kg. Most compounds showed slower on-set and longer duration of action relative to cocaine. Surprisingly, 3beta-(4-methylphenyl)-2beta-[3-(4'-chlorophenyl)isoxazol-5-yl]tropane (3p) and 3beta-(4-methylphenyl)-2beta-[3-(4'-methylphenyl)isoxazol-5-yl]tropane (3r) did not produce significant increases in locomotor activity. In the cocaine discrimination test, all analogues showed full or at least 50% generalization with the exception of 3p, which did not show generalization. Importantly, both the locomotor activity and the cocaine discrimination ED(50)values were correlated with the DAT binding but not 5-HTT and NET binding. This provides further support for the dopamine hypothesis of cocaine abuse. High DAT affinity and selectivity, increased locomotor activity with slow onset and long duration of action, and generalization to cocaine shown by the 3beta-(substituted phenyl)-2beta-(3-substituted isoxazol-5-yl)tropanes are properties thought necessary for a pharmacotherapy for treating cocaine abuse.     

Chronic lithium treatment decreases neuronal activity in the nucleus accumbens and cingulate cortex of the rat.

Although the efficacy of lithium as a mood stabilizer is well documented, the mechanism of its therapeutic effect associated with prolonged treatment remains unknown. Identifying discrete brain regions and neural pathways that are functionally altered following long-term lithium treatment is central to elucidating a psychotherapeutic mechanism. We have used a sensitive and quantitative histochemical assay for the determination of cytochrome oxidase (CO) activity, a mitochondrial marker of neuronal activity, to determine the effect of repeated lithium treatment on regional neuronal activity in the rat brain. Oral lithium treatment (21 days) selectively decreased cytochrome oxidase activity in the cingulate cortex and regions of the nucleus accumbens. These decreases were not seen after 5 days of lithium administration, although serum lithium concentrations were similar after both 5 and 21 days of treatment. The analysis of interregional correlations further suggests a role for amygdala pathways in the effects of lithium following 21 days of treatment. The implications of these data for understanding the mechanisms of action of lithium are discussed.     

Fabrication of a Fixed Retrievable Implant‐supported Prosthesis Based on Electroforming: A Technical Report

This article describes a method of fabricating a fixed retrievable implant‐retained prosthesis based on electroforming. This method combines the advantages of both the cement‐ and screw‐retained prostheses, including passive fit, ease of fabrication, and retrievability. The absence of visible occlusal screw‐canals adds to its increased esthetic appeal.     

3H]cocaine binding and inhibition of [3H]dopamine uptake is similar in both the rat striatum and nucleus accumbens

Cocaine binds with high affinity to the dopamine transporter in both the striatum and the nucleus accumbens. We examined Na(+)-dependent [3H]cocaine binding, mazindol inhibition of [3H]cocaine binding and cocaine inhibition of [3H]dopamine uptake in both rat brain areas. The striatum and nucleus accumbens demonstrated Na(+)-dependent [3H]cocaine binding with similar densities. Mazindol inhibited [3H]cocaine binding with a similar IC50 in both the striatum and nucleus accumbens. Likewise, cocaine inhibited [3H]dopamine uptake in both brain regions with equivalent efficacy. From these data we conclude that the dopamine transporter is similar in both the striatum and nucleus accumbens.     

Beta-adrenergic receptors in human trabecular meshwork. Identification and autoradiographic localization

Beta-adrenergic receptors were identified in slide-mounted sections of human trabecular meshwork by in-vitro labeling, light microscopic autoradiography. Autoradiograms were generated after incubation of slide-mounted tissue sections with 125I-cyanopindolol, a selective high-affinity probe for beta-adrenergic receptors. Experiments in which an excess of either unlabeled Practolol (beta 1 selective ligand) or Zinterol (beta 2 selective ligand) were included suggested that most of the receptors were of the beta 2 subtype. Data from displacement studies using increasing concentrations of the highly specific beta 1- and beta 2-adrenergic receptor antagonists, ICI-89,406 and ICI-118,551, respectively, confirmed the predominance of the beta 2-adrenergic receptors. Similar results obtained with cultured trabecular endothelial cells suggest that the beta-adrenergic receptors may be associated with the endothelial cells of the trabecular meshwork in vivo. These results provide anatomic evidence for the hypothesis that beta-adrenergic agents improve outflow by direct action on the trabecular meshwork and provide a rationale for the development of more selective beta 2-adrenergic agents to increase outflow facility.