Stimulus control and compounding with ambient odor as a discriminative stimulus on a free-operant baseline.

Previous experiments have demonstrated that the simultaneous presentation of independently established discriminative stimuli can control rates of operant responding substantially higher than the rates occasioned by the individual stimuli. This "additive summation" phenomenon has been shown with a variety of different reinforcers (e.g., food, water, shock avoidance, cocaine, and heroin). Discriminative stimuli previously used in such studies have been limited to the visual and auditory sensory modalities. The present experiment sought to (1) establish stimulus control on a free-operant baseline with an ambient olfactory discriminative stimulus, (2) compare olfactory control to that produced with an auditory discriminative stimulus, and (3) determine whether compounding independently established olfactory and auditory discriminative stimuli produces additive summation. Rats lever pressed for food on a variable-interval schedule in the presence of either a tone or an odor, with comparable control developed to each stimulus. In the absence of these stimuli responding was not reinforced. During stimulus compounding tests, the tone-plus-odor compound occasioned more than double the responses occasioned by either the tone or odor presented individually. Thus, the current study (1) established stimulus control with an ambient olfactory discriminative stimulus in a traditional free-operant setting and (2) extended the generality of stimulus-compounding effects by demonstrating additive summation when olfactory and auditory discriminative stimuli were presented simultaneously.

Recovery from ischemic brain injury in the rat following a 10 h delayed injection with MLN519.

In the present study, we evaluated delayed treatment effects of the proteasome inhibitor and anti-inflammatory agent MLN519 (initiated 10 h post-injury) to improve recovery following ischemic brain injury in rodents. Male rats were exposed to 2 h of middle cerebral artery occlusion (MCAo) and treated with MLN519 (1.0 mg/kg, i.v. @ 10, 24, and 48 h post-occlusion) or vehicle. By 2 weeks post-injury, 60% (6/10) of vehicle animals survived, which was improved (although non-significantly) to 78% (7/9) following MLN519 treatment. The percent loss of tissue in the ipsilateral brain hemisphere (at 2 weeks) was significantly reduced from 27+/-4% (vehicle) to 15+/-4% (MLN519). MLN519 treated animals also lost significantly less body weight (39%) and showed significant improvement in overall neurological function across the 2-week recovery period. However, no significant treatment effects were observed to reduce foot-fault deficits (balance beam) or improve recovery of operant performance (active avoidance test). Overall, delayed treatment with MLN519 provided significant improvement in 3 of 6 test metrics (histopathology, body weight, and neurological dysfunction) supporting improved outcome for brain-injured subjects.

Stimulus control of cocaine self-administration.

Environmental stimuli that set the occasion wherein drugs are acquired can "trigger" drug-related behavior. Investigating the stimulus control of drug self-administration in laboratory animals should help us better understand this aspect of human drug abuse. Stimulus control of cocaine self-administration was generated here for the first time using multiple and chained schedules with short, frequently-alternating components--like those typically used to study food-maintained responding. The procedures and results are presented along with case histories to illustrate the strategies used to produce this stimulus control. All these multicomponent schedules contained variable-interval (VI) components as well as differential-reinforcement-of-other-behavior (DRO) or extinction components. Schedule parameters and unit dose were adjusted for each rat to produce stable, moderate rates in VI components, with minimal postreinforcement (infusion) pausing, and response cessation in extinction and DRO components. Whole-body drug levels on terminal baselines calculated retrospectively revealed that all rats maintained fairly stable drug levels (mean, 2.3 to 3.4 mg/kg) and molar rates of intake (approximately 6.0 mg/kg/hr). Within this range, no relation between local VI response rates and drug level was found. The stimulus control revealed in cumulative records was indistinguishable from that achieved with food under these schedules, suggesting that common mechanisms may underlie the control of cocaine- and food-maintained behavior.