Effects of intraperitoneal carbon monoxide on fixed-ratio and screen-test performance in the mouse.

The behavioral effects of carbon monoxide (CO) administered via IP injection were investigated in the mouse. Mice were trained to lever press under a fixed-ratio (FR) 100 schedule of water reinforcement. Thirty-min test sessions were conducted either immediately or 30 min following IP injections of air (100 ml/kg) or CO (7.5, 15, 30, 50 or 100 ml/kg). CO produced a decrease in rates of responding which was exhibited earlier and lasted longer with increasing doses. Motor performance was also measured with the inverted-screen test following the same doses of CO at either 5, 15, 30, 60, 120 min or 24 hr post-injection. Performance was affected in a dose- and time-dependent fashion. Peak carboxyhemoglobin (COHb) levels were observed at 15 or 30 min and were 20%, 32%, 42%, 51% and 60% for 7.5, 15, 30, 50 and 100 ml/kg CO, respectively. COHb saturation alone was not always a good predictor of behavioral effects since both level and duration of exposure contributed to behavioral impairment. The results also show that the IP route can be used to study the toxicity of CO.

Separation of the response rate and discriminative stimulus effects of phencyclidine: training dose as a factor in phencyclidine-saline discrimination.

The training dose was progressively reduced (faded) using rats in a drug discrimination task in order to determine whether the discriminative stimulus effects of phencyclidine HCI (PCP) were separable from its response rate effects. Rats were initially trained to discriminate PCP from saline in a two-lever food-reinforced operant discrimination procedure. After initial training at 3.0 mg/kg, the rats were subsequently retrained at 1.5, 0.75 and 0.375 mg/kg. Stimulus generalization testing followed training at each training dose. Although discriminative control was developed by lower doses of PCP during the fading procedures, control by previously effective higher doses was not diminished. The number of training sessions required before reaching criterion levels of performance and the number of errors during training (i.e., incorrect lever selections) increased with decreases in training dose. The results indicated that fading of the training dose of PCP caused marked parallel shifts in the dose-effect curves for PCP's discriminative stimulus effects although its response rate effects were left unaffected. The ED50 for PCP's discriminative stimulus effects decreased with decreases in training dose although the ratio of the ED50 to the training dose remained relatively constant. The ED50 for the response rate effects, however, remained relatively constant with decreases in training dose, and the ratio of the ED50 to the training dose markedly increased. It was concluded that the discriminative stimulus and the response rate effects of PCP are separable and, hence are under control by different determinants.