Drugs online research references
Psychopharmacology (Berl). 1987;93(2):139-45.
Discriminative stimulus properties of muscarinic agonists.
Jung M, Costa L, Shearman GT, Kelly PH.
Preclinical Research, Sandoz A.G., Basel, Switzerland.
In a two-lever, food-reinforced drug-discrimination paradigm separate groups of rats were trained to discriminate either arecoline, pilocarpine or oxotremorine from saline. The discriminative cues of all three agonists were potently blocked by scopolamine, but only by 30-60 fold higher doses of methylscopolamine. The three agonists all suppressed overall response rate. These rate-suppressant effects were not blocked by scopolamine in doses which blocked the discriminative cues. In generalization tests, arecoline elicited selection of the drug-appropriate lever in all groups of trained animals. Pilocarpine was discriminated as drug by all pilocarpine-trained animals and by a majority of oxotremorine-trained animals, but was not significantly discriminated by the arecoline-trained group. Oxotremorine was discriminated by all oxotremorine-trained animals but only by some pilocarpine-trained animals, and was not significantly discriminated by the arecoline-trained group. Morphine, haloperidol, chlordiazepoxide, pentobarbital and nicotine were not generalized to any of the training drugs. The discriminative stimuli produced by the training drugs are therefore specific and exhibit properties indicative of an origin at central muscarinic receptors but may not be identical.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3122245&dopt=Abstract
Eur J Pharmacol. 1988 Aug 9;153(1):97-104.
Discriminative stimulus properties of physostigmine in rats.
Tang AH, Franklin SR.
CNS Diseases Research, Upjohn Company, Kalamazoo, MI 49001.
Sprague-Dawley rats were trained to discriminate a subcutaneous injection of physostigmine (0.2 mg/kg) from a similar injection of saline in a two-lever, food-reinforced behavior paradigm. The training dose of physostigmine reduced the response rate to about 50% of that in saline sessions. The discriminative stimulus (DS) effect of physostigmine is mediated by a central cholinergic mechanism since it was antagonized by scopolamine (0.1 mg/kg), but was unaffected by methylscopolamine (1 mg/kg) or pirenzepine (3 mg/kg). Neostigmine produced predominantly saline-appropriate lever choice. Compounds which produced averages of greater than 80% responses on the physostigmine lever are: compound BM-5 (N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)-acetamide), tetrahydroaminoacridine (THA), RS-86 (2-ethyl-8-methyl-2,8-diazaspiro-(4,5)-decan-1,3-dion hydrobromide), cis-AF30 (2-methyl-spiro-(1,3-dioxolane-4,3')-quinuclidine), and pilocarpine. In comparison, oxotremorine, aceclidine (3-acetoxy-quinuclidine), arecoline, and nicotine produced a maximum average responding of 40-70% on the physostigmine lever. The DS effect of physostigmine in rats appeared to involve a greater participation of M1 and M2 muscarinic or the nicotinic receptor in the brain.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3215280&dopt=Abstract
Brain Res. 1983 Jan 17;259(1):111-8.
Paradoxical reinforcing properties of apomorphine: effects of nucleus accumbens and area postrema lesions.
van der Kooy D, Swerdlow NR, Koob GF.
Apomorphine (0.01-10.0 mg/kg, subcutaneously) paradoxically produced both dose-dependent aversive and positive reinforcing effects, as measured in conditioned taste aversion and place preference paradigms, respectively. The conditioned taste aversions produced by apomorphine were not modified in rats with bilateral 6-hydroxydopamine (6-OHDA) lesions of the nucleus accumbens (producing 92% depletion of dopamine in the nucleus accumbens) nor in rats with thermal lesions of the area postrema. Both types of lesions were behaviorally verified as effective in other paradigms; the 6-OHDA lesions potentiated the facilitatory effects to a novel flavor paired with scopolamine methylnitrate (1.0 mg/kg, intraperitoneally). However, 6-OHDA lesions of the nucleus accumbens did clearly potentiate the conditioned place preferences induced by apomorphine. These results suggest that both the positive reinforcing and locomotor effects of apomorphine may partially result from activation of post-synaptic dopamine receptors in the nucleus accumbens. Moreover, the dissociation of apomorphine's aversive and positive reinforcing properties revealed by the 6-OHDA lesions may provide the first step in attempts to pinpoint the different brain sites of action where apomorphine produces its opposite motivational effects.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6824923&dopt=Abstract
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