Dopamine transporter binding without cocaine-like behavioral effects: synthesis and evaluation of benztropine analogs alone and in combination with cocaine in rodents.

Rationale: Previous SAR studies demonstrated that small halogen substitutions on the diphenylether system of benztropine (BZT), such as a para-Cl group, retained high affinity at the cocaine binding site on the dopamine transporter. Despite this high affinity, the compounds generally had behavioral effects different from those of cocaine. However, compounds with meta-Cl substitutions had effects more similar to those of cocaine.

Discriminative stimulus effects of putative D3 dopamine receptor agonists in rats.

Three separate groups of rats were trained to discriminate the putative D3 dopamine receptor agonists (+/-)-7-hydroxydipropylaminotetralin (7-OH-DPAT) (0.03 mg/kg), PD 128,907 (1.0 mg/kg) and quinpirole (0.

Choice under concurrent VI schedules: comparison of behavior maintained by cocaine or food.

Previous research has shown that concurrent schedule responding maintained by cocaine under short variable-interval (VI) schedules is well described by the generalized matching law. That is, drug-maintained behavior was apportioned in accordance with relative frequency of reinforcement. The purpose of the present experiment was to examine the ability of the generalized matching law to account for choice under longer VI schedules of cocaine availability, and to compare cocaine-maintained to food-maintained behavior in this regard.

Characterization of unconditioned behavioral effects of dopamine D3/D2 receptor agonists.

A series of experiments examined the ability of dopamine D3/D2 receptor agonists [(+)-(4aR,10bR)-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]b enzopyrano-[4,3-b]-1,4-oxazin-9-ol hydrochloride (PD 128,907), (+/-)-7-hydroxy-dipropylaminotetralin hydrobromide (7-OH-DPAT), quinpirole and bromocriptine] to produce a variety of dopaminergically mediated behaviors. The effects of these drugs with selectivity for D3/D2 receptors over D1 receptors were compared with those produced by the selective D1 agonists [(+/-)-Phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride (SKF 38393), (+/-)-6-Chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-be nzazepine hydrobromide (SKF 82958)], a nonselective dopaminergic agonist (apomorphine), and an indirect dopamine agonist (cocaine). The D3/D2 agonists decreased locomotor activity, had no effect on gnawing and only inconsistently induced climbing in mice.

Assessment of cocaine-like discriminative stimulus effects of dopamine D3 receptor ligands.

The highly selective dopamine D3 receptor ligand, (+)-PD 128907 4aR10bR-(+)-trans-3,4,4a,10b-tetrahydro-4-n-propyl-2H5H[4,3- b]-1,4- oxazin-9-ol), and other dopamine D3 receptor ligands, (+/-)-7-hydroxy-2-(N,N-di-n-propylamino)tetralin and (+)-7-hydroxy-2-(N,N-di-n-propylamino)tetralin, substituted for the discriminative stimulus effects of cocaine in rats, an animal model of subjective effects in humans. Substitution only occurred at doses that markedly decreased responding. These results suggest that dopamine D3 receptors may be involved in the subjective effects of cocaine, and therefore may be a target for the discovery of treatments for cocaine dependence.

The effects of differing response-force requirements on fixed-ratio responding of rats.

Rats were exposed to two-component multiple schedules of food delivery. In the first experiment, 15 responses were required to produce food in both components. A downward force of 0.

Pharmacological analysis of the scratching produced by dopamine D2 agonists in squirrel monkeys.

Several dopamine agonists, administered i.m., produced persistent, excessive and non-localized scratching in squirrel monkeys (Saimiri sciureus).

Effects of D1 dopamine agonists on schedule-controlled behavior in the squirrel monkey.

Behavioral effects of several dopamine D1 receptor agonists were compared with those of cocaine and (+)-amphetamine in squirrel monkeys trained to press a response key under a fixed-interval schedule of electric shock presentation. Cocaine (0.03 to 0.

Effects of cocaine on fixed-ratio responding of rats: modulation by required response force.

The effects of acute cocaine administrations (5.6-32 mg/kg) were determined in rats responding under a multiple fixed-ratio 15 (FR 15) FR 15 schedule of food delivery. The minimum response effort required in one schedule component was 25 g, whereas in the other component it was 200 g.

Self- and cross-citations in the Journal of Applied Behavior Analysis and the Journal of the Experimental Analysis of Behavior: 1983-1992.

We examined self- and cross-citation practices in JABA and JEAB from 1983 through 1992. Mean levels of self-citation for JABA and for JEAB were 22.6% and 36.

Fixed-ratio size as a determinant of tolerance to cocaine: is relative or absolute size important?

Six studies, examining five drugs in three species, have demonstrated that tolerance development is impaired under relatively long fixed-ratio (FR) schedules compared with relatively short FR schedules. One such study demonstrated that substantial tolerance to the rate-reducing effects of cocaine in pigeons developed under the FR 5 and 25 components of a multiple schedule of food delivery, but little or no tolerance developed under the FR 125 component. The present study examined the acute and chronic effects of cocaine in three groups of pigeons.

Effects of d-amphetamine and ethosuximide on responding under delayed-matching-to-sample procedures with differential and nondifferential outcomes.

Pigeons were exposed to delayed-matching-to-sample (DMTS) procedures in which food or a flash of the feeder light followed correct responses. When these consequences were correlated with a particular stimulus (e.g.

The effects of phenobarbital on responding under delayed-matching-to-sample procedures with differential and nondifferential outcomes.

Pigeons were exposed to delayed-matching-to-sample procedures in which food or a flash of the feeder light followed correct responses. When these consequences were correlated with a particular stimulus (e.g.

Free birds aren't fat: Weight gain in captured wild pigeons maintained under laboratory conditions.

Nine feral pigeons, 5 from an urban setting and 4 from a rural setting, were captured and maintained for 42 days under free-feeding conditions comparable to those arranged for laboratory subjects. On average, birds increased their body weights by 17% over this period. The range of increase across birds was 9 to 30%.

A program for normal glycemic control of insulin-dependent diabetes.

A method of instruction enabling patients to control their diabetes is described. The patients learn through home glucose monitoring how their blood sugar levels vary with changes in diet, exercise, and insulin. They learn to chart accurately all the factors influencing their control in a manner that enables them, as well as the physician, to analyze them quickly.