Thèse--Sc. nat.--Paris, 1958. / Thèse soutenue sous le titre : "Détermination du groupement chimique responsable de l'activité sympathicolytique de la yohimbine" Bibliogr. p. 93-112. Index. Tiré à 50 ex.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1956. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves [92-93]).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1955. / Typescript. Abstracted in dissertation abstracts, v. 16 (1956) no. 2, p. 243. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 94-95).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1957. / Typescript. Abstracted in dissertation abstracts, v. 17 (1957) no. 7, p. 1471-1472. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 98-100).

It has been proposed that relapse vulnerability in previously dependent individuals results from augmentation of drug-induced reinforcement due to repeated associations between the interoceptive properties of the drug and reduction of acute withdrawal distress. To test this hypothesis, male Sprague-Dawley rats self-administered 0.05 mg/kg/inf heroin on continuous and progressive ratio (PR) schedules. During this period, they also received injections of vehicle or escalating doses of heroin. Following tests of naloxone-precipitated withdrawal (0.01 or 0.1 mg/kg, SC), as well as abstinence (4 days), and extinction training (9 sessions), they were pre-treated with vehicle or yohimbine (0.5 mg/kg, IV) and tested for resumption of heroin self-administration (0.05 mg/kg/inf) on continuous and PR schedules (Experiments 1 & 2), or tested for reinstatement in extinction conditions. Differences between vehicle- and heroin-injected rats were noted on self-administration on the continuous reinforcement schedule, but not on the PR schedule, in spite of greater signs of withdrawal precipitated by naloxone in the heroin-injected rats. More importantly, there were no group differences in resumption of heroin self-administration, and this was not altered by yohimbine. These results suggest that relapse vulnerability cannot be uniquely ascribed to the altered reinforcing action of drugs; contextual and other conditioning factors must play a role in modulating resumption of drug intake after periods abstinence.

Rapid eye movement sleep decreases between 10 and 30 days postnatally in the rat. The pedunculopontine nucleus is known to modulate waking and rapid eye movement sleep, and pedunculopontine nucleus neurons are thought to be hyperpolarized by noradrenergic input from the locus coeruleus. The goal of the study was to investigate the possibility that a change in α-2 adrenergic inhibition of pedunculopontine nucleus cells during this period could explain at least part of the developmental decrease in rapid eye movement sleep. We, therefore, recorded intracellularly in 12-21 day rat brainstem slices maintained in oxygenated artificial cerebrospinal fluid. Putative cholinergic vs. non-cholinergic pedunculopontine nucleus neurons were identified using nicotinamide adenine dinucleotide phosphate diaphorase histochemistry and intracellular injection of neurobiotin (Texas Red immunocytochemistry). Pedunculopontine nucleus neurons also were identified by intrinsic membrane properties, type I (low threshold spike), type II (A) and type III (A+low threshold spike), as previously described. Clonidine (20 μM) hyperpolarized most cholinergic and non-cholinergic pedunculopontine nucleus cells. This hyperpolarization decreased significantly in amplitude (mean±S.E.) from -6.8±1.0 mV at 12-13 days, to -3.0±0.7 mV at 20-21 days. However, much of these early effects (12-15 days) were indirect such that direct effects (tested following sodium channel blockade with tetrodotoxin (0.3 μM)) resulted in hyperpolarization averaging -3.4±0.5 mV, similar to that evident at 16-21 days. Non-cholinergic cells were less hyperpolarized than cholinergic cells at 12-13 days (-1.6±0.3 mV), but equally hyperpolarized at 20-21 days (-3.3±1.3 mV). In those cells tested, hyperpolarization was blocked by yohimbine, an α-2 adrenergic receptor antagonist (1.5 μM). These results suggest that the α-2 adrenergic receptor on cholinergic pedunculopontine nucleus neurons activated by clonidine may play only a modest role, if any, in the developmental decrease in rapid eye movement sleep. Clonidine blocked or reduced the hyperpolarization-activated inward cation conductance, so that its effects on the firing rate of a specific population of pedunculopontine nucleus neurons could be significant. In conclusion, the α-2 adrenergic input to pedunculopontine nucleus neurons appears to consistently modulate the firing rate of cholinergic and non-cholinergic pedunculopontine nucleus neurons, with important effects on the regulation of sleep-wake states.

Montréal Trigonix inc. 2018

The indole alkaloids, a class of natural products, have received much synthetic attention for years due to their diverse structures and interesting biological properties. We are particularly interested in synthesizing some of the yohimbine alkaloids extracted from the bark of a tall evergreen African tree (Corynanthe yohimbe, commonly known as fringe tree). Yohimbine and its stereoisomers have been tempting targets for synthetic organic chemists for more than fifty years. These compounds feature a pentacyclic ring system with two heteroatoms and five stereogenic centers. Broadly, the fifteen different synthetic approaches that led to the successful completion of yohimbine alkaloids relied only on two basic synthetic strategies. In the first strategy, the last step almost always was the formation of the C(2)-C(3) bond by either Pictet-Spengler reaction or by Bischler-Napieralski reaction with the concomitant formation of the C ring. The second strategy involved the annulation of the D and E rings onto the intact ABC ring system. With our double annulation methodology, herein, we report a completely different synthetic approach to access the yohimbine alkaloids, and our disconnections are not even remotely close to the synthetic designs used in the past. Our key steps include double Michael reaction to construct the E ring, an intramolecular cyclization to construct the D ring, and finally, the functionality on the D ring can be elaborated to form the C ring of the yohimbine alkaloids.

Thesis (Ph. D. in Neuroscience)--Vanderbilt University, Aug. 2009. / Title from title screen. Includes bibliographical references.

Indiana University-Purdue University Indianapolis (IUPUI) / Stress has been shown to contribute to alcohol drinking; however, inconsistencies in both the clinical and pre-clinical literature speak to the need for better paradigms to study this interaction. The present experiments compared animal models of the propensity to consume ethanol, the selectively bred alcohol-preferring (P) and high-alcohol-drinking (HAD) rat lines, in their response to yohimbine on ethanol seeking and self-administration and anxiety-like behavior. The P and HAD lines consume similar amounts of ethanol, yet differ in apparent motivation to drink ethanol, in anxiety-like behavior, and response to stress in alcohol drinking. Therefore, it was of interest to determine whether stress may differentially affect ethanol-motivated behaviors between the P and HAD lines. Acute administration of yohimbine, an α-2 adrenoreceptor antagonist that increases anxiety and activate stress systems, increased operant ethanol self-administration and reinstatement of ethanol seeking in P rats, and free-choice ethanol drinking in both P and HAD rats. However, acute yohimbine administration decreased ethanol drinking when given limited access in the home cage, an effect that was diminished by extending the pre-treatment interval or increasing the number of ethanol exposure sessions. Yohimbine did not alter appetitive responding during a non-reinforced trial, nor did yohimbine alter the acquisition of free-choice ethanol drinking. Exposure to alcohol deprivation resulted in modest increases in ethanol intake, but yohimbine did not potentiate this effect. While acute yohimbine administration increased anxiety-like behavior, prior experience with repeated yohimbine exposures or with repeated deprivation periods did not. P rats were shown to be more active and less anxious and to display greater responding during a non-reinforced trial than HAD rats. Taken together, the results of these experiments demonstrate that the timing of yohimbine exposure relative to ethanol access is a critical component to determining its effects on ethanol seeking and self-administration and anxiety-like behavior. Further investigation into the parameters under which stress alters the motivation to seek and consume ethanol between these selectively bred lines is warranted, and future work that incorporates therapeutic agents aimed at reducing stress reactivity and alcohol drinking could elucidate effective strategies in the treatment of alcoholism.