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Biomedical subjects

W J Lynch

Publications and source records attributed to W J Lynch.

At least 19 recordsLinked to original sources

Effects of sex and the estrous cycle on regulation of intravenously self-administered cocaine in rats.

RATIONALE: Previous research with both humans and animals suggests that there are sex differences in cocaine self-administration; in rodents, ovarian hormones may underlie these differences. OBJECTIVES: A two-lever drug self-administration procedure was used to compare regulation of intravenously self-administered cocaine in male and female rats and among females in different phases of the estrous cycle. METHODS: Eleven female and seven male age-matched Wistar rats were trained to self-administer nine doses of cocaine (0.0-2.4 mg/kg) during daily 5-h sessions. Experimental test chambers were equipped with two levers and associated stimulus lights. A response on the lever with stimuli signaling an increase in cocaine dose increased the infusion duration by 3 s, and a response on the other lever decreased the infusion duration by 3 s. RESULTS: After responding for cocaine stabilized, regulation was disrupted more in females than in males (r2=78.9, r2=92.6, respectively) with the greatest disruption observed in females during the estrus phase (r2=48.5). Mean dose size varied considerably for males and for females in the metestrus/diestrus and proestrus phases; however, estrus females responded almost exclusively on the lever associated with an increase in cocaine dose. CONCLUSIONS: These findings indicate sex differences in the regulation of cocaine self-administration, and they suggest that ovarian hormones may be responsible for the observed sex differences.

Animals↗

Reinstatement of cocaine self-administration in rats: sex differences.

RATIONALE: Results obtained with both humans and animals suggest that rates of relapse, or levels of reinstatement responding, may differ between males and females. However, the results obtained with humans are equivocal, and few studies have compared male and female animals on reinstatement responding. OBJECTIVES: The present experiment was designed to compare male (n=8) and female (n=8) rats on reinstatement of extinguished cocaine-reinforced responding. METHODS: Reinstatement of responding was examined using a priming model in which lever pressing for cocaine (0.2 mg/kg) was extinguished by replacing cocaine infusions (2 h) with saline infusions (5 h). After responding extinguished during hour 3, reinstatement of responding was tested by administering one of several priming injections of cocaine (0.32, 1.0 and 3.2 mg/kg) or an equal volume of saline. RESULTS: Although males and females did not differ in the number of saline infusions self-administered after either saline or 0.32 mg/kg cocaine-priming injections, female rats self-administered significantly more saline infusions than males after 1.0 mg/kg and 3.2 mg/kg cocaine-priming injections. Additionally, the effects of 0.32 mg/kg cocaine-priming injections were significantly different from those of saline-priming injections for female, but not male, rats. There was no significant difference between males and females in total cocaine self-administered during hours 1 and 2. CONCLUSIONS: These findings indicate that female rats are more sensitive than males during the reinstatement phase of drug abuse.

Analysis of Variance↗

Transurethral microwave thermotherapy: symptom relief v urodynamic changes.

Transurethral microwave thermotherapy (TUMT), whether in its low- or high-energy form, seems to reduce the symptoms of benign prostatic hyperplasia, with low-energy treatment resulting in less improvement than high-energy treatment. Low-energy TUMT has a minimal effect on bladder outlet obstruction, as judged by urodynamic findings, and may not be suitable to treat those patients with significant obstruction. High-energy TUMT does seem to relieve obstruction significantly, although it is not as effective as TURP. Urodynamic studies may provide the answer as to which therapy to offer the patient.

Dose-Response Relationship, Radiation↗

Sex differences in the acquisition of intravenously self-administered cocaine and heroin in rats.

RATIONALE: Despite numerous reports that male and female animals differ in behavioral responses to drugs, few studies have investigated sex differences in drug-reinforced behavior. OBJECTIVES: Acquisition of IV cocaine and heroin self-administration was compared in 20 female and 22 male Wistar rats. METHODS: An autoshaping procedure was used to train rats to press a lever that resulted in either a 0.2 mg/kg infusion of cocaine or a 0.015 mg/kg infusion of heroin under a fixed-ratio 1 (FR 1) schedule. Daily sessions consisted of six 1-h autoshaping components followed by a 6-h self-administration component. During each autoshaping component, a retractable lever briefly (15 s) extended into the test chamber on a random interval schedule with a mean of either 90 s (cocaine groups) or 480 s (heroin groups) and either ten (cocaine groups) or five (heroin groups) computer-automated infusions were delivered each hour. During each 6-h self-administration component, the lever remained extended and each response on the lever resulted in an infusion of either cocaine (0.2 mg/kg) or heroin (0.015 mg/kg). The criterion for acquisition of cocaine self-administration was a mean of at least 100 infusions and the criterion for heroin self-administration was a mean of at least 20 infusions during the self-administration component over five consecutive sessions. RESULTS: Female rats acquired both cocaine and heroin self-administration more rapidly than males. Acquisition of cocaine self-administration occurred in a greater percentage of female rats compared to males. Female rats self-administered more cocaine than males after acquisition criteria had been met. CONCLUSIONS: These findings indicate that female rats were more vulnerable than males to the acquisition of cocaine and heroin self-administration under the conditions of the present experiment.

Animals↗

Regulation of intravenously self-administered nicotine in rats.

Ten male Wistar rats had access to 9 doses of nicotine (0.01-0.10 mg/kg i.v.) during daily 5-hr sessions. Once responding for nicotine stabilized, nicotine infusions were replaced with either cocaine infusions (0.0-2.4 mg/kg) or saline infusions. Saline substitution results indicate that nicotine functioned as a reinforcer. Regulation of nicotine intake was compared with that of cocaine by obtaining the correlation between mean interdose interval and preceding dose size. Results reveal that although this correlation was significant for both nicotine and cocaine self-administration, nicotine self-administration was less precisely regulated than cocaine self-administration. This procedure suggests that there are differences in regulation among self-administered drugs and that it may serve as a useful baseline for studying differences in vulnerability to drug abuse and potential treatment strategies.

Animals↗

The effects of restraint stress on voluntary ethanol consumption in rats.

Sixty Wistar rats (Rattus norvegicus) were assigned to 4 groups of 15 rats each: ethanol stress (ES), ethanol no-stress (EN), isocaloric stress (IS) and isocaloric no-stress (IN). The effect of restraint stress on daily intake of ethanol and a 0.72% solution of glucose was examined in an ABA design (stress-no stress-stress). During the stress phases, 2 groups were subjected to daily 15-min restraint stress, whereas 2 groups were placed in different cages for 15 min as a control. All 4 groups were then given 6-hr access to their assigned liquid alone for 4 days followed by a choice between their assigned liquid and water on the 5th day. The ES group significantly increased their ethanol intake (g/kg) compared to the EN group on choice days but not on forced days. Percentage preference for ethanol was significantly greater and increased at a faster rate over the 75-day testing period compared with the EN group. However, total ethanol consumption (g/kg) and percentage preference did not vary as a function of phase. It is notable that the effects of restraint stress on ethanol self-administration persisted even after the stress schedule was removed.

Alcohol Drinking↗

Evaluation of interstitial diode laser therapy for treatment of benign prostatic hyperplasia.

In the last decade, a number of new device technologies were developed for benign prostatic hyperplasia (BPH) therapy. These technologies were introduced in an effort to reduce the morbidity of BPH therapy associated with conventional electrocautery transurethral resection of the prostate (TURP). While morbidity is reduced, the aim of new therapy is to achieve near equivalence in efficacy of outcome measures, namely, improved voided flow rate and reduced symptom score. To gain acceptance by urologists, these technologies should be easy to apply and should reduce the economic cost of BPH treatment. The Indigo 830e diode laser system offers simplified laser therapy from a miniaturized solid-state system. This pilot study demonstrates outcome equivalence to TURP in preliminary evaluation and shows an acceptable side effect profile.

Aged↗

A novel paradigm to investigate regulation of drug intake in rats self-administering cocaine or heroin intravenously.

The purpose of this experiment was to investigate the regulation of drug intake in rats (n = 20) self-administering heroin or cocaine during daily 5-hr sessions. Operant chambers were equipped with 2 levers and associated stimulus lights. A response on the lever with stimuli signaling an increase in dose size increased the infusion duration by 3 s, and a response on the lever with stimuli signaling a decrease in dose size decreased the infusion duration by 3 s. Results showed that daily and hourly drug intake for cocaine and heroin groups were relatively constant. Significant correlation coefficients were obtained for heroin and cocaine groups for the relationship between interdose interval (IDI) and infusion duration (dose size). These findings indicate that subjects regulated their drug intake by adjusting IDI throughout drug self-administration sessions.

Animals↗

Effects of amphetamine, butorphanol, and morphine pretreatment on the maintenance and reinstatement of cocaine-reinforced responding.

Three groups of rats (N = 23) self-administered intravenous cocaine (0.4 mg/kg/infusion) during the initial 2 hr of daily 7-hr sessions. During the remaining 5 hr of these sessions, responding produced saline infusions. On test days, each rat was pretreated with an assigned dose of either butorphanol, morphine, amphetamine, or saline before the self-administration session followed by a priming injection of cocaine (3.2 mg/kg i.v.) or saline at the beginning of the 4th hr. Results showed that both amphetamine (0.5, 1.0, and 2.0 mg/kg) and morphine (0.3, 1.0, and 2.0 mg/kg) pretreatment dose-dependently reduced cocaine self-administration whereas only amphetamine affected (increased) reinstatement responding. Butorphanol pretreatment (8 mg/kg) suppressed cocaine self-administration and blocked the effect of the cocaine priming injections on pretreatment testing days. These findings indicate that (a) pretreatment drugs with similar stimulus properties potentiate reinstatement of responding and (b) pretreatment drugs can differentially affect maintenance and reinstatement of responding.

Amphetamine↗

Ethanol consumption in rats when dose size is under subject control.

Rats orally self-administered ethanol when they could control dose size as follows: A lever press initiated a trial; a press on 1 lever increased the previous trial duration by 30% whereas a press on a 2nd lever decreased the previous trial duration by 30%. During a trial, rats could drink either water, 8%, or 16% (wt/vol) ethanol (ETOH) from a lick-sensitive fountain. Mean per session intake of 8% and 16% ETOH was 0.8 g/kg and 1.3 g/kg, respectively. Water intake was negligible. Rats did not show a tendency to maintain a particular trial duration, nor did they adjust intertrial intervals to previous dose size (number of licks). When trials were collected into bouts, a positive relationship was found between bout size and interbout interval; this relationship was statistically significant for the 8% but not the 16% ETOH condition.

Alcohol Drinking↗

Renal cryotherapy in a sheep model; a feasibility study.

PURPOSE: This study was designed to evaluate the safety and efficacy of renal cryotherapy as a possible treatment of renal malignancy with preservation of renal parenchyma. MATERIALS AND METHODS: Ten Merino sheep were anaesthetised and the right kidney was exposed through a retro-peritoneal approach. A 5 mm. cryotherapy probe (LCS 3000 Cryotec UK) was inserted into the lower pole of the kidney and freezing was undertaken to form an iceball 5 cm. in diameter. RESULTS: There was no mortality and no complications were observed. A transient rise in creatinine was observed post-operatively. The sheep were euthenased at 4 weeks and at necropsy macroscopic examination revealed a contracted, fibrotic wedge shaped lesion of 3 cm in diameter. Histological examination of the "cryolesion" revealed a central area of coagulative necrosis and a 5 mm rim of partial necrosis with preservation of renal tubules. CONCLUSION: We conclude that renal cryotherapy is safe and can achieve effective renal necrosis in the sheep model.

Animals↗