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The neurochemical and behavioral effects produced by drugs can differ based on whether self-administered or experimenter-administered. In addition, self-administered drugs, particularly those taken orally or by inhalation, have peripheral stimulus effects that are not present following experimenter administration. One drug with highly prominent peripheral stimulus effects when taken orally is ethanol. The purpose of the present experiment was to examine whether orally self-administered (SA) ethanol would serve as a discriminative stimulus and to determine if the peripheral effects of ethanol play a major role in the discriminative stimulus of orally SA ethanol. Twelve Long-Evans rats were trained to orally self-administer 750 mg/kg of 10% (w/v) ethanol and then discriminate that dose of ethanol from SA water. Six of twelve rats were successfully trained to discriminate oral SA ethanol from water. Intraperitoneal experimenter-administered and orally SA ethanol doses of 100–1320 mg/kg were tested for substitution. SA and i.p. ethanol doses of 750, 1000, and 1320 mg/kg fully substituted for the SA training dose. SA doses of 100, 320 and 560 mg/kg partially substituted for the SA ethanol training dose, whereas the 100 and 320 mg/kg i.p. ethanol doses did not substitute for SA ethanol. The ED 50 values for SA and i.p. ethanol were not significantly different from one another. The results indicate that SA ethanol can serve as a discriminative stimulus in rats and that i.p. ethanol can substitute for SA ethanol. In addition, the results also show that the discriminative stimulus effects of SA ethanol are primarily mediated by CNS drug effects.

Studies report a high incidence of alcohol abuse in methadone maintenance patients. There is, however, little data on the reinforcing effects of combinations of ethanol and methadone. In the present study, oral self-administration of a combination of 1% (w/v) ethanol and 0.2 mg/ml methadone was compared to each drug alone in three rhesus monkeys in which methadone alone was not a reinforcer. In Experiment 1, ethanol and the combination, but not methadone alone, served as reinforcers. In Experiment 2, there was no preference for ethanol or the combination at fixed ratio (FR) 8 or 16. When the FR size was doubled (FR 16 or 32), all three animals preferred the combination to 1% ethanol. Experiment 3 further examined the effect of work requirement on preference for ethanol or the combination by varying FR values [1, 2, 4, 8, 16, or 32]. At lower FRs, ethanol was significantly preferred to the combination. As FR was increased, there was a significant reduction in preference for ethanol over the combination. The results show that an ethanol + methadone combination will be orally self-administered by monkeys and suggest that work requirement differentially modifies preference for the combination and ethanol alone.

Responses of rhesus monkeys were reinforced by delivery of either a pentobarbital (4.0 mg/ml) solution or a vehicle (water) or saccharin solution under a concurrent signaled differential reinforcement of low rates 30-s schedule. After 30 s of no responding, the first response on the pentobarbital or saccharin spout resulted in the delivery of the appropriate solution and reset the timing on both spouts (i.e. a mutually exclusive choice). In the first experiment, the concentration of saccharin was gradually increased across sessions. As saccharin concentration increased, pentobarbital deliveries decreased and saccharin as well as total session deliveries increased. In a second experiment, pentobarbital and 0.24 (mg/ml) saccharin were made available under concurrent signaled differential reinforcement of low rates 30-s schedules which operated independently. Under these conditions responding on one spout had no consequences with respect to the other spout. The reduction of pentobarbital deliveries was substantially attenuated when the choice was not mutually exclusive.

Twelve pigeons key-pecked under a multiple variable interval 15-second, variable interval 150-second schedule of food reinforcement. Effects of two opioid drugs, buprenorphine and methadone, were determined alone and in combination with chronic daily administration of the antidepressants doxepin or bupropion. Methadone initially produced dose-dependent key-pecking rate reductions when administered acutely, prior to the session, while buprenorphine produced key-pecking rates that reached a plateau at 50-80% of baseline rate and were not reduced further by higher doses. Neither doxepin nor bupropion, given alone, had lasting effects on key-pecking rates. Chronic daily doxepin administration significantly attenuated methadone-induced response rate reductions. Bupropion reduced the effect of the highest methadone dose, but this effect was mitigated by the development of opioid tolerance. Unlike bupropion, doxepin interfered with the development of opioid tolerance. Neither antidepressant systematically altered effects of buprenorphine on key-pecking.

Study Design. Records of 111 patients randomly selected from a population who received an interbody fusion cage during a clinical Investigation Device Exemption trial (BAK/L) yielded 126 operative levels and were retrospectively assessed. Objectives. This study examined lumbar spine sagittal alignment and clinical outcomes before and 2 years after fusion surgery. Summary of Background Data. Lumbar lordosis is important in spinal sagittal alignment and balance, especially the L4–S1 area. Perceived consensus is that anatomically correct lumbar lordosis is desired and that a loss of lumbar lordosis may lead to spine pathology. There is little information on lumbar lordosis after interbody fusion. Methods. A random sample of 111 patients who received a cylindrical cage implant (total pool of 947 patients) yielded 126 operative lumbar segments. There were 52 posterior approaches and 59 anterior approaches, and all cages were placed in the L4–L5 or L5–S1 levels. Preoperative and 2-year follow-up lateral radiographs were measured for segmental lordosis. Cage position was measured relative to the posterior longitudinal ligament. Segmental lordotic change was correlated to clinical outcome at the 2-year follow-up. Results. Preoperative lordosis was different as a function of surgical approach. There was a significant 2-year decrease in lordosis with the posterior approach group; however, all intervertebral angles were within typical ranges. Clinical outcomes were significantly improved 2 years postsurgery. There was no correlation between changes in lordosis and clinical outcomes. Conclusions. Interbody lumbar fusion with a threaded cylindrical cage does not appear to have any clinically relevant effects on segmental lordosis, which is maintained within anatomically normal levels. Clinical outcome measures show significant postsurgery improvement, and changes in lordotic angles are not predictive of clinical outcome.

Seven rats lever pressed under a progressive ratio 3 (PR 3) schedule of food presentation; the number of responses per reinforcer systematically increased during each session. Break point (i.e., the number of responses in the last completed ratio before session termination) was measured under daily methadone (4.5 mg/kg and 3.0 mg/kg) or buprenorphine (0.3 mg/kg) administered prior to experimental sessions. Both drugs initially eliminated rats' food-maintained progressive-ratio responding. Break points during chronic methadone did not return to baseline levels after 80 drug sessions and a dose reduction. In contrast, break points during chronic buprenorphine administration were considerably above baseline control levels for two rats and returned to baseline levels for the third.

Oral cocaine self-administration was studied in water-deprived Lewis rats. Liquid was available to rats only during daily 90-min sessions, in chambers equipped with spouts that delivered precise volumes of liquid following completion of lever-press responses. Blocks of training and testing sessions were alternately carried out during which increasing cocaine concentrations were presented: 0.0, 0.0125, 0.025, 0.05, 0.1, 0.2, 0.282, and 0.4 mg/ml. Although high cocaine intakes (23.3-33.0 mg/kg) were obtained, neither avoidance nor preference for cocaine developed. Subsequently, fixed-ratio size was increased, and then distinctive stimulus lights were correlated with each liquid. One rat showed a preference for water following these changes, but two rats continued to show no preference. To determine if the amounts of cocaine self-administered had behavioral effects, locomotor activity tests were run immediately following self-administration sessions. Locomotor activity was substantially higher following cocaine self-administration than following water self-administration. These results demonstrate that the cocaine intakes reached under the present conditions did produce locomotor, but not reinforcing, effects.

Rodents will typically consume greater amounts of low concentration ethanol (1-6%) than water. However, few primate oral self-administration studies have examined low ethanol concentrations. Additionally, there is a scarcity of data showing ethanol-maintained behavior without using induction procedures in either rats or primates. In this study, 14, free-feeding, naive, adult, male rhesus monkeys were given access to a 2% (w/v) ethanol solution and vehicle (tap water) during daily 3-hour sessions. Water was freely available between sessions. Liquids were available under a concurrent fixed-ratio four reinforcement schedule; thus, four responses (mouth-spout contacts) on either spout were immediately followed by the delivery of approximately 0.65 ml of liquid. In phase 1, tap water was available from both spouts. In phase 2, vehicle and a 2% ethanol solution were concurrently available. The 2% ethanol solution maintained considerably higher response rates than vehicle for 12 of 14 monkeys. In phase 3, food intake was limited. During this phase, the 2% ethanol solution maintained significantly higher response rates than vehicle for all monkeys. Additionally, during phase 3, ethanol intakes were greater than those in phase 2 for all monkeys. Central drug effects and taste factors are discussed. These results demonstrate that ethanol will serve as a reinforcer for naive rhesus monkeys in the absence of induction procedures.