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PubMed1993

Evaluation of the reinforcing and discriminative stimulus effects of cocaine in combination with (+)-AJ76 or clozapine.

Because self-administration and discrimination of a drug by animals correlate with its abuse and subjective effects in humans, interventions that modify the reinforcing and discriminative stimulus effects of the drug may be useful in the treatment of its abuse. The present study was designed to evaluate the effects of the putative dopamine autoreceptor antagonist (+)-AJ76 (AJ) or the atypical antipsychotic clozapine (CLZ) on the reinforcing and discriminative stimulus effects of cocaine in monkeys. One group of rhesus monkeys (n = 6) was allowed to self-administer cocaine (0.03 or 0.1 mg/kg/injection i.v. fixed-ratio 10, 2 hr/day). A second group of monkeys (n = 5) was trained to discriminate cocaine (0.2 or 0.4 mg/kg i.m., 10 min presession) from saline in a two lever, food-reinforced, drug discrimination paradigm. When behavior was stable, AJ or CLZ was administered i.m., 15 or 30 min presession. Intermediate doses of both compounds (1.0-3.0 mg/kg of AJ; 0.3-1.0 mg/kg of CLZ) increased cocaine self-administration, while responding remained evenly distributed over the session. A higher dose of CLZ decreased cocaine self-administration in an apparently nonspecific manner. When combined with saline, partial substitution for cocaine was seen in one of three monkeys with AJ and in none with CLZ. In combination with the training dose of cocaine in the discrimination experiment, both AJ and CLZ decreased drug appropriate responding by at least 50% in two of four monkeys, but had little or no effect in the other monkeys up to doses that completely suppressed lever pressing (6.4 mg/kg of AJ; 3.2 mg/kg of CLZ). Taken together, the present findings suggest that any blockade of the reinforcing and discriminative stimulus effects of cocaine by AJ and CLZ was, at best, partial. Furthermore, the stimulant effects of AJ observed in rats were not prominent in monkeys.

Animals↗
PubMed1996

Chronic d-amphetamine or methamphetamine produces cross-tolerance to the discriminative and reinforcing stimulus effects of cocaine.

These experiments tested the hypothesis that chronic administration of d-amphetamine (d-A) or methamphetamine (METH) would produce cross-tolerance to the discriminative and/or reinforcing effects of cocaine. One group of rats (n = 20) was trained to detect cocaine (10.0 mg/kg; i.p.) from vehicle; cocaine (1.0-17.8 mg/kg) dose dependently substituted for the training dose. Chronic administration of d-A or METH (0.32, 1.0 and 3.2 mg/kg/12 hr for 7 days) resulted in cross-tolerance to the discriminative stimulus effects of cocaine. A second group of rats (n = 12) was implanted with indwelling jugular catheters and were trained to self-administer cocaine under a fixed-ratio 2 schedule of reinforcement. This group of rats also received chronic d-A or METH (0.32, 1.0 and 3.2 mg/kg/12 hr for 7 days. In this group, chronic administration of the highest dose of d-A and of METH (3.2 mg/kg) resulted in cross-tolerance to the self-administration of cocaine. A third group of rats (n = 15) was implanted with indwelling jugular catheters and were trained to self-administer cocaine under a progressive-ratio schedule of reinforcement. Chronic administration of d-A and METH (3.2 mg/kg/12 hr for 7 days) resulted in cross-tolerance to the self-administration of cocaine under this progressive-ratio schedule. The data obtained from these experiments demonstrate that chronic treatment with central nervous system stimulants of the amphetamine type (d-A or METH) produces cross-tolerance to both the discriminative and reinforcing effects of cocaine.

Animals↗
PubMedDate not supplied

[The systems process of reinforcement].

The process of reinforcement is considered in the context of the general theory of functional systems as an important part of behavioural act organization closely interacting with the dominant motivation. It is shown that reinforcement substantially changes the activities of separate neurons in different brain structures involved in dominant motivation. After a preliminary reinforcement under the influence of corresponding motivation the ribosomal apparatus of neurons begins to synthesize special molecular engrams of the action acceptor. The sensory mechanisms of reinforcement and, especially, the role of emotions are considered in details in the paper.

Animals↗
PubMed1996

Behavior-relevant changes in nucleus accumbens dopamine transmission elicited by food reinforcement: an electrochemical study in rat.

Voltammetry was used to monitor dopamine (DA) transmission in nucleus accumbens (NAcc) of rats lever-pressing for food. Under standard conditions, animals responded on a fixed ratio 1 (FR1) schedule for 0.2 ml of milk delivered over 30 sec; milk delivery was paired with a 30 sec cue light. Consumption of the initial few milk rewards of the session caused DA signal increases. These initial signal increases were typical of the first and, at times, the second test days. On subsequent days, the most pronounced initial signal increases coincided with presentation of conditioned stimuli that marked the start of the session. Biphasic changes in DA signal that were time-locked to each reinforced lever-press were also observed; responses were preceded by increases and were followed, during milk consumption, by decreases in DA signal. At the end of milk delivery, the signal increased again in apparent anticipation of the next lever-press. Delaying milk delivery caused a corresponding delay in DA signal decreases, and the amount of time signals remained depressed was bound by the duration of milk consumption. Greater decreases in DA signal were observed when the rate of milk delivery was doubled or tripled, and such increases in reward value were associated with more pronounced signal increases during the period that preceded each lever-press. In contrast, DA signal increases were seen when milk was delivered at half the usual rate or was withheld altogether or when animals were denied access to the lever. Under partial reinforcement conditions, reinforced lever-presses were preceded by more pronounced signal increases and decreases of comparable magnitude accompanied milk consumption. These results suggest that meso-NAcc DA neurons are activated primarily in response to the incentive rather than to the reinforcing properties of rewards.

Animal Feed↗
PubMedDate not supplied

[The concept of reinforcement in research on simple nervous systems].

Analysis of applicability of the reinforcement concept to the learning studies in invertebrate systems is performed basing on literature and own data. It is suggested that reinforcement can be regarded not as an independent phenomenon, but as a state of the nervous system which precedes a long-term changes of behavior. Such consideration of reinforcement allows to use this concept in studies of plasticity and learning in simple nervous systems, investigate neurochemical mechanisms of reinforcement.

Animals↗
PubMedDate not supplied

[Interneuronal frontal-amygdala interactions in cats trained for the quality of the reinforcement].

In eight cats the appetitive instrumental conditioned reflexes to light were elaborated by the method of "active choice" of reinforcement quality: the short-latency bar-pressing responses were reinforced with bread-meat mixture and the delayed responses were reinforced with meat. The animals differed in behavior strategy: six cats preferred the delayed pressings (the so-called "self-control" group), and two cats preferred the pressings with short delay (the so-called "impulsive" group). The multiunit activity in the basolateral amygdala and frontal cortex was recorded by chronically implanted nichrome semimicroelectrodes. The interactions of the neighboring neurons in the basolateral amygdala and the frontal cortex (within the local neuronal networks) and between the amygdalar and cortical neurons (distributed neuronal networks of amygdalar-frontal and fronto-amygdalar directions) were estimated by means of statistical crosscorrelation analysis of spike trains. The interneuronal cross-correlations were studied with delays in the range of 0-100 ms. The number of cross-correlations between the neuronal discharges both in the local and distributed networks was significantly higher in "impulsive" cats, mainly, with delays in the range of 0-30 ms. In both groups of animals the number of correlations was the highest during omissions of conditioned pressings, i.e., in cases of difficult choice of reinforcement. We suggest that the basolateral amygdala, frontal cortex, and amygdalar-frontal distributed neuronal networks are involved in the system of brain structures, which determine the individual features of animal behavior.

Amygdala↗
PubMed1998

The reinforcing effects of ethanol are altered by the endogenous neurosteroid, allopregnanolone.

We examined the effect of systemic administration of the endogenously occurring progesterone metabolite, allopregnanolone, on oral self-administration of ethanol by male rats. Rats were trained to perform an operant response for presentation of 0.1 ml of a solution of 10% ethanol in water using the sucrose fading technique. After acquisition of stable lever-press responding on a fixed-ratio 4 schedule, subjects received subcutaneous injections of 1, 3, or 10 mg/kg of allopregnanolone, or vehicle, 20 min prior to the self-administration session. Pretreatment with 3 mg/kg, but not 1 or 10 mg/kg, increased the mean total number of lever press responses made to obtain ethanol, and therefore increased the mean total number of ethanol presentations. The number of responses and response rate were examined as a function of the number of "runs" within the 30-min session; a "run" was defined as a series of consecutive responses with an interresponse interval of <1 min. The increase in total responses after 3 mg/kg was due in part to an increased number of responses for the first run of the session, with no effect on response rates. However, the higher dose of 10 mg/kg decreased response rates within the first run. Thus, allopregnanolone alters ethanol-reinforced responding at concentrations lower than those that depress rates of responding. The effects of administration of the benzodiazepene, diazepam, were determined for comparison with those of the neurosteroid. The subcutaneous injection of 0.3, 1.0, or 3.0 mg/kg of diazepam did not produce any clear dose-dependent changes in measures of ethanol-reinforced operant responding, supporting the suggestion of differences in the contribution of the benzodiazepene and neurosteroid binding sites to GABA(A) receptor function. The results indicate that exogenous administration of allopregnanolone dose-dependently alters ethanol-reinforced operant responding, and suggest that this endogenously occurring neurosteroid could mediate some of the reinforcing effects of ethanol.

Alcohol Drinking↗
PubMed1964

REINFORCEMENT AS INPUT: CYCLIC VARIABLE-INTERVAL SCHEDULE.

Daily exposure of pigeons to four cycles of a reinforcement schedule in which the density of reinforcements varied cyclically as a function of time induced a periodicity in their responding matching that of the schedule, but out of phase with it. The technique used of presenting the same sequence of interreinforcement intervals in every session may have useful application in determining animals' adjustment to more complex temporal patterns of reinforcement. Investigation of animals' response to cyclic schedules of different frequencies suggests links with engineering methods of frequency analysis.

Animals↗
PubMed1963

Ratio reinforcement of matching behavior.

Three pigeons, previously trained to a high level of accuracy on matching-to-sample procedures, were exposed to various schedules of ratio reinforcement for correct matches. Overall accuracy was lower on fixed ratio than on regular reinforcement. There was a high incidence of errors immediately after reinforcement on fixed ratio schedules with accuracy increasing as the ratio progressed. This increase was found to be inversely correlated with the latency of the observing response to the sample. By contrast, accuracy was high throughout the ratio on a variable ratio schedule.

Animals↗
PubMed1963

Behavioral effects of pairing an S-D with a decreasing limited-hold reinforcement schedule.

Four pigeons were trained on a multiple reinforcement schedule consisting of two limited-hold schedules, one in which a discriminative stimulus (S(D)) accompanied the periodic reinforcement contingency, and one in which the discriminative stimulus was omitted. The duration of the limited-hold in each component of the multiple schedule was reduced in parallel steps. It was shown that behavioral differences between the two schedules were attenuated by this manipulation of temporal parameters. When S(D) was reduced in duration, three out of four pigeons responded with extremely high S(Delta) rates, despite the regular pairing of S(Delta) with the reinforcement contingency. These high rates qualitatively resembled the rapid rates emitted on the analogous no-S(D) component.

Animals↗
PubMed1964

STIMULUS GENERALIZATION AND THE RESPONSE-REINFORCEMENT CONTINGENCY.

Generalization gradients along a line-tilt continuum were obtained from groups of pigeons that had been trained to peck a key on different schedules of reinforcement. In Exp. I, gradients following training on a differential-reinforcement-of-low-rate (DRL) schedule proved to be much flatter than gradients following the usual 1-min variable interval (VI) training. In Exp. II, the value of the VI schedule itself was parametrically studied; Ss trained on long VI schedules (e.g., 4-min) produced much flatter gradients than Ss trained on short VI schedules (30-sec; 1-min). The results were interpreted mainly in terms of the relative control exerted by internal, proprioceptive cues on the different reinforcement schedules. Several implications of the results for other problems in the field of stimulus generalization are discussed.

Animals↗
PubMed2005

Dopamine and serotonin neurotransmission in the reinforcing effects of alcohol and apomorphine.

OBJECTIVE: To determine the role of dopamine and 5-hydroxytryptamine (5-HT; serotonin) in the reinforcing effects of alcohol and apomorphine. DESIGN: Experimental study. PLACE AND DURATION OF STUDY: Department of Biochemistry, University of Karachi from September to November 2004. SUBJECTS AND METHODS: The study was conducted on 24 male albino Wistar rats. Reinforcing effects were monitored in a conditioned place preference (CPP) paradigm using a light-dark activity box. Slicing and punching method was used to collect dorsal and ventral striatum. Neurochemical estimations were done by HPLC-EC. RESULTS: Withdrawal from repeated administration of ethanol (1g/kg/day) as well as apomorphine (1 mg/kg/day) elicited reinforcement that could be monitored in a CPP paradigm. CNS depressant effects of ethanol were not altered on repeated administration but CNS stimulatory effects of apomorphine increased. Reinforcing effects of ethanol but not apomorphine were associated with a decrease in dopamine metabolism in the ventral striatum. CONCLUSION: A decrease in the activity of dopaminergic neurons following withdrawal from repeated administration is involved in the compulsive use of abused drugs.

Animals↗
PubMedDate not supplied

Alar expansion and reinforcement: a new technique to manage nasal valve collapse.

OBJECTIVE: To describe the new technique of alar expansion and reinforcement as a comprehensive approach to the surgical management of nasal valve collapse. METHODS: Alar expansion and reinforcement expands the narrow nasal valve and reinforces the floppy nasal sidewall. Forty-one patients underwent rhinoplastic surgery for nasal valve collapse between May 1, 2002, and April 30, 2005, using an external rhinoplasty approach; of these, 32 responded to our postoperative questionnaire. Twenty-four patients (75%) underwent primary surgery and 8 (25%) had undergone previous rhinoplasty. All patients had permanent adjustable expansion sutures. Twelve patients (38%) had an excessively floppy nasal sidewall that required a high-density porous polyethylene alar batten implant to anchor the expansion sutures. Patients underwent clinical review from 6 months to 3 years after surgery, and a telephone survey was used to evaluate their functional and cosmetic satisfaction rates. RESULTS: Thirty patients (94%) experienced good improvement in their nasal airway. The improvement in nasal airway patency was statistically significant (P<.001). Two patients (6%) reported no improvement. There were no complications. Cosmetic outcome was satisfactory in all 8 patients who also requested cosmetic improvement. Of the 24 patients who had surgery for nasal obstruction only, 10 (42%) rated their cosmetic appearance as better, with the remaining 14 (58%) indicating that they did not identify any significant change in their nasal appearance. CONCLUSION: Alar expansion and reinforcement is a safe, reliable, and effective technique to manage nasal valve collapse.

Adult↗
PubMed1993

Effects of scleral reinforcement on the elongation of growing cat eyes.

OBJECTIVE: We investigated the effect of scleral reinforcement on ocular elongation in the rapidly growing eyes of juvenile cats. METHODS: Bands made from donor sclera or expanded polytetrafluoroethylene were used to reinforce one eye of each animal; contralateral eyes underwent sham surgery. RESULTS: During 5 months of follow-up, normal intraocular pressures implied normal functioning of angle structures. A-scan on the central axis showed no difference in globe lengths. Direct physical measurements of the posterior aspect of the globe at enucleation revealed significant decreases in off-center lengthening where reinforcement was present compared with unreinforced areas in the same eyes and in the contralateral unbanded eyes. Venous beading in fundus photographs of three eyes suggested impairment of venous outflow. CONCLUSIONS: Scleral reinforcement appears to control expansion of the growing cat eye to a limited extent, but the effects on vision and retinal perfusion require further investigation.

Animals↗
PubMed2005

Glycolide copolymer staple-line reinforcement reduces staple site bleeding during laparoscopic gastric bypass: a prospective randomized trial.

HYPOTHESIS: The use of staple-line reinforcement sleeves during laparoscopic gastric bypass reduces staple-line bleeding, which may translate into a reduction in the rate of gastrointestinal hemorrhage. DESIGN: Prospective randomized trial. SETTING: University hospital. PATIENTS AND INTERVENTIONS: Thirty-four patients undergoing laparoscopic gastric bypass were randomly assigned to receive either no reinforcement (control group, n = 17) or reinforcement of the staple line with glycolic copolymer sleeves (treatment group, n = 17). MAIN OUTCOME MEASURES: Demographic data, the number of stapler loads used, the number of staple-line bleeding sites, the amount of blood loss, the length of time required to obtain hemostasis of the staple lines, operative time, intraoperative and postoperative complications, and serial hemoglobin levels. RESULTS: The mean number of stapler loads used was similar between groups. The mean number of staple-line bleeding sites was significantly fewer in the treatment group for division of gastric tissue (0.4 vs 2.5 bleeding sites), jejunal tissue (0.1 vs 0.6 bleeding site), and mesenteric tissue (0 vs 0.8 bleeding site). The mean blood loss was lower in the treatment group (84 vs 129 mL). Staple misfire occurred in 1 (0.7%) of 143 stapler loads used in the treatment group compared with 0 (0%) of 138 stapler loads used in the control group. The time to obtain staple-line hemostasis was shorter in the treatment group (1.2 vs 10.1 minutes). The total operative time was similar between groups. There was no mortality or postoperative leaks. One patient in the control group had postoperative gastrointestinal hemorrhage requiring blood transfusion and reoperation. There was no significant difference in the mean hemoglobin level between groups on the first postoperative day. CONCLUSIONS: The use of glycolide copolymer staple-line reinforcement sleeves in patients undergoing laparoscopic gastric bypass is safe and significantly reduces staple-line bleeding sites and may reduce the incidence of gastrointestinal hemorrhage.

Adult↗
PubMed2000

Whisker-reinforced dental core buildup composites: effect of filler level on mechanical properties.

The strength and toughness of dental core buildup composites in large stress-bearing restorations need to be improved to reduce the incidence of fracture due to stresses from chewing and clenching. The aims of the present study were to develop novel core buildup composites reinforced with ceramic whiskers, to examine the effect of filler level, and to investigate the reinforcement mechanisms. Silica particles were fused onto the whiskers to facilitate silanization and to roughen the whisker surface for improved retention in the matrix. Filler level was varied from 0 to 70%. Flexural strength, compressive strength, and fracture toughness of the composites were measured. A nano-indentation system was used to measure elastic modulus and hardness. Scanning electron microscopy (SEM) was used to examine the fracture surfaces of specimens. Whisker filler level had significant effects on composite properties. The flexural strength in MPa (mean +/- SD; n = 6) increased from (95+/-15) for the unfilled resin to (193+/- 8) for the composite with 50% filler level, then slightly decreased to (176+/-12) at 70% filler level. The compressive strength increased from (149+/-33) for the unfilled resin to (282+/-48) at 10% filler level, and remained equivalent from 10 to 70% filler level. Both the modulus and hardness increased monotonically with filler level. In conclusion, silica particle-fused ceramic single-crystalline whiskers significantly reinforced dental core buildup composites. The reinforcement mechanisms appeared to be crack deflection and bridging by the whiskers. Whisker filler level had significant effects on the flexural strength, compressive strength, elastic modulus, and hardness of composites.

Bisphenol A-Glycidyl Methacrylate↗
PubMed2001

Strong and macroporous calcium phosphate cement: Effects of porosity and fiber reinforcement on mechanical properties.

Because of its excellent osteoconductivity and bone-replacement capability, self-setting calcium phosphate cement (CPC) has been used in a number of clinical procedures. For more rapid resorption and concomitant osseointegration, methods were desired to build macropores into CPC; however, this decreased its mechanical properties. The aims of this study, therefore, were to use fibers to strengthen macroporous CPC and to investigate the effects of the pore volume fraction on its mechanical properties. Water-soluble mannitol crystals were incorporated into CPC paste; the set CPC was then immersed in water to dissolve mannitol, producing macropores. Mannitol/(mannitol + CPC powder) mass fractions of 0, 10, 20, 30, and 40% were used. An aramid fiber volume fraction of 6% was incorporated into the CPC-mannitol specimens, which were set in 3 mm x 4 mm x 25 mm molds and then fractured in three-point flexure to measure the strength, work of fracture, and modulus. The dissolution of mannitol created well-formed macropores, with CPC at 40% mannitol having a total porosity of a 70.8% volume fraction. Increasing the mannitol content significantly decreased the properties of CPC without fibers (analysis of variance; p < 0.001). The strength (mean +/- standard deviation; n = 6) of CPC at 0% mannitol was 15.0 +/- 1.8 MPa; at 40% mannitol, it decreased to 1.4 +/- 0.4 MPa. Fiber reinforcement improved the properties, with the strength increasing threefold at 0% mannitol, sevenfold at 30% mannitol, and nearly fourfold at 40% mannitol. The work of fracture increased by 2 orders of magnitude, but the modulus was not changed as a result of fiber reinforcement. A scanning electron microscopy examination of specimens indicated crack deflection and bridging by fibers, matrix multiple cracking, and frictional pullout of fibers as the reinforcement mechanisms. Macroporous CPCs were substantially strengthened and toughened via fiber reinforcement. This may help extend the use of CPCs with macropores for bony ingrowth to the repair of larger defects in stress-bearing locations.

Algorithms↗
PubMed1994

Materials and design concepts for an intervertebral disc spacer. I. fiber-reinforced composite design.

The intervertebral disc is a complex joint anatomically and functionally. It may be displaced or damaged due to trauma or a disease process. To alleviate this condition, it may be necessary to remove the involved disc surgically and fuse the two adjacent vertebrae. Fusion is one option; however, replacing the damaged disc (or part thereof) with a suitable synthetic equivalent to allow near normal joint motion is more desirable. Unfortunately, the complex mechanical properties of the lumbar disc cannot be duplicated with homogeneous synthetic materials (polymers). To overcome this fundamental problem we have developed rational designs utilizing biocompatible thermoplastic elastomers of various stiffnesses (durometers) with and without fiber reinforcements. Our design consisted of three components analogous to the natural end plates, annulus, and nucleus. In this study only the fiber-reinforced design is considered. The variables examined in the present study included orientation of the fiber layers, number of fiber layers, and order of the reinforcing layers. The results of mechanical testing of the fiber reinforced disc spacer indicate that the range of compressive and torsional properties can be achieved. The results further demonstrate that properly developed, this design results in properties similar to the natural disc. Designs developed provided adequate compression and compression torsion properties for a synthetic spine disc spacer.

Biocompatible Materials↗