NICOTINE SELF-ADMINISTRATION IN MONKEYS *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74815/1/j.1749-6632.1967.tb13730.x.pd

Levels and distribution of central nervous system amines in normal and morphine-dependent monkeys

The distribution of norepinephrine, dopamine and 5-hydroxytryptamine in various areas of the CNS of the normal monkey has been presented.The central levels and distribution of norepinephrine, dopamine and 5-hydroxytryptamine were determined after single doses of morphine, during maintenance of physical dependence and following withdrawal from chronic administration of morphine. Small and non-stressful doses of morphine were employed to induce experimental physical dependence.Alpha-methyl-DOPA did not qualitatively or quantitatively alter the abstinence syndrome.Pretreatment with iproniazid did not prevent depression produced by single doses of morphine in the non-tolerant monkey.The data observed in this study offer no support for the view that gross behavioral changes in the monkey produced by morphine or by its withdrawal after the development of physical dependence are induced by or may be correlated with changes in amine levels in the CNS.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34146/1/0000431.pd

A comparison of the pharmacology of two potent analgesic agents, piminodine (Win 14,098-2) and Win 13,797, with morphine and meperidine

The toxic and lethal effects of piminodine and Win 13,797 were studied in mice, dogs, and monkeys. The analgesic actions of both drugs were tested in mice and rats and were found to be more potent than morphine.Vascular studies on pimincdine and Win 13,797 have shown peripheral vasodilation and acute vascular tolerance to the hypotensive effect in dogs with partial crossed tolerance to morphine. Dogs anesthetized with pentobarbital were sensitive to the respiratory depressant actions of these drugs. Nalorphine readily antagonizes this respiratory depression.Piminodine and Win 13,797 are myocardial depressants on the dog heart-lung preparation and the cat papillary muscle, but only in doses or concentrations much higher than would be used therapeutically.The actions of piminodine and Win 13,797 on the isolated rabbit jejunal segment are minimal.The qualitative actions of piminodine and Win 13,797 on EEG effects in dogs with chronically implanted electrodes were like those of morphine. Quantitatively, Win 13,797 was equipotent to morphine, and piminodine one-half as effective.Studies on single-dose suppression in monkey and primary physical dependence in dogs and monkeys indicate that piminodine and Win 13,797 have high addiction liability at least in these species.Nearly all the administered piminodine or Win 13,797 is altered chemically when injected into dogs. There is no evidence for marked local tissue deposition for either drug.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32367/1/0000442.pd

Self-administration of psychoactive substances by the monkey

A method has been developed which permits monkeys to self-administer drug solutions, at will, through indwelling intravenous catheters. Psychological dependence on the effects of a drug occurs when a naive monkey voluntarily initiates and maintains self-administration of the drug. If, in addition to psychological dependence, the drug also produces psychotoxicity, either directly or upon abrupt withdrawal, it has a potential abuse liability.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46354/1/213_2004_Article_BF00405254.pd

An Analysis Of The Factors Influencing The Development Of Physical Dependence To Narcotic Analgesics In The Rhesus Monkey With Methods For Predicting Physical Dependence Liability In Man.

PhDPharmacologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/181833/2/5800900.pd

Stimulant and motivational effects of alcohol: Lessons from rodent and primate models

In several animal species including humans, the acute administration of low doses of alcohol increasesmotor activity. Different theories have postulated that alcohol-induced hyperactivity is causally related to alcoholism.Moreover, a common biological mechanism in the mesolimbic dopamine system has been proposed to mediate the stimulant and motivational effects of alcohol. Numerous studies have examined whether alcohol-induced hyperactivity is related to alcoholism using a great variety of animal models and several animal species. However, there is no review that has summarized this extensive literature. In this article, we present the various experimental models that have been used to study the relationship between the stimulant and motivational effects of alcohol in rodents and primates. Furthermore, we discuss whether the theories hypothesizing a causal link between alcohol-induced hyperactivity and alcoholism are supported by published results. The reviewed findings indicate that animal species that are stimulated by alcohol also exhibit alcohol preference. Additionally, the role of dopamine in alcohol-induced hyperactivity is well established since blocking dopaminergic activity suppresses the stimulant effects of alcohol. However, dopamine transmission plays a much more complex function in the motivational properties of alcohol and the neuronal mechanisms involved in alcohol stimulation and reward are distinct. Overall, the current review provides mixed support for theories suggesting that the stimulant effects of alcohol are related to alcoholism and highlights the importance of animal models as a way to gain insight into alcoholism