Vincent P. Houser

Activity and food-restriction effects on gastric glandular lesions in the rat: The activity-stress ulcer

Eighteen rats, 60 days old, and 18 rats, 110 days old, were housed in standard activity cages and fed 1 h each day for 21 days. Ten rats, 60 days old, and five rats, 110 days old, died before the end of the experiment. All rats that died revealed extensive lesions in glandular portions of the stomach. Control rats, housed in standard cages and also fed 1 h each day, did not die. Experimental rats that died were more active than experimental rats that survived, and ate less than survivors and normal control rats. This technique is proposed as a new animal model for studying gastrointestinal pathology.

Analgesic potency of sodium salicylate, indomethacin, and chlordiazepoxide as measured by the spatial preference technique in the rat

The analgesic potency of various doses of sodium salicylate (150, 200, 250, 300, 350 mg/kg), indomethacin (1.5, 2.0, 2.5, 3.0, 3.5, 5.0 mg/kg) and chlordiazepoxide (2.5, 5.0, 10.0, 20.0 mg/kg) were measured using the spatial preference technique. All three agents were active in a wide range of doses indicating that this technique is sensitive to the weak analgesics. The chlordiazepoxide data were interpreted to suggest that this tranquilizing agent may be able to impair the appreciation of the emotional (i.e., aversive) qualities of electric shock, thus reducing the animals motivation to escape the noxious stimulus. A procedure for computing ED50 estimates was also presented along with a summary of the ED50 values for several standard narcotic and narcotic antagonist analgesics. Since this procedure is a reliable and sensitive index of drug-induced analgesia, it should be useful as a screening procedure in evaluating the analgesic potency of a wide variety of chemical agents.

Modulation of the aversive qualities of shock through a central inhibitory cholinergic system in the rat

Evidence has been supplied which suggests that a central inhibitory cholingeric (i.e., muscarinic) system may be involved in modulating the aversive qualities of electric shock in the rat. Central cholinergic stimulation via the administration of pilocarpine or arecoline the threshold for grid shock, while central acting anticholinergics (i.e., scopolamine and atropine) produced decrements in the threshold. Peripheral acting anticholinergics (e.g., methyl scopolamine, methyl atropine) were less potent than central acting drugs given in equivalent doses, while peripheral cholinergic stimulants (i.e., neostigmine, carbachol) were inactive. In addition, only the central acting stimulant pilocarpine, and not carbachol, was able to block the decrements noted in response to scopolamine hydrobromide administration. Finally, only arecoline, and not nicotine, was able to elevate the aversive threshold indicating that muscarinic receptor sites are probably involved in mediating the effects of central cholinergic stimulants.

The effects of scopolamine and pilocarpine upon the aversive threshold of the rat

Abstract The analgesic potency of scopolamine hydrobromide (0.125, 0.250, 0.50, 1.0, 2.0 mg/kg) and pilocarpine nitrate (1.25, 2.50, 5.0, 10.0 mg/kg) were measured in the rat using the spatial preference technique. Only pilocarpine nitrate in doses at or above 2.50 mg/kg significantly raised the aversive threshold. These data were interpreted to indicate that cholinergic systems may be involved in the production of analgesia in the rat. The present results may be useful in interpreting the behavioral effects of cholinergic drugs administered to animals that are under the control of aversive schedules of reinforcement.

A method for determining the aversive threshold in the rat using repeated measures: Tests with morphine sulfate

The procedure described here provides an objective automated technique for the psychophysical assessment of the aversive threshold and allows the animal Ss to serve as their own controls. Sensitivity to drug effects, as well as comparisons between drugs, using the same animals are possible also. Using a rectangular tilt cage, the aversive threshold to grid shock was defined as that intensity avoided 75% of the time. Each shock intensity (30, 60, 90, 120, and 150 microA) was presented for 5 min on one side of the cage and then switched to the other side for 5 min, thereby forcing the animal to sample each shock intensity. Aversive thresholds were determined daily for each rat. The analgesic effects of morphine sulfate were compared to saline. Animals were tested for 3 days at each morphine dose level (2, 4, 8, and 16 mg/kg). Each 3-day morphine series alternated with 3 days of testing under saline. Significant differences were detected between saline and morphine at 4, 8, and 16 mg/kg.

An electronic constant current shock generator for low current levels

Abstract A simple, low cost electronic shock generator capable of producing constant current 60 Hz square wave outputs between 15–200 μA is described. The unit is designed using a penta-grid converter tube which regulates extremely well at low current levels. A circuit diagram is included along with a detailed description of the performance characteristics of this generator. The unit is capable of maintaining a constant current across an animal even when the animals resistance alters radically as when shock is applied to a moving animal through a grid. The unit is extremely useful in obtaining sensory or motivational thresholds in small animals.

Modulation of avoidance behavior in squirrel monkeys after chronic administration and withdrawal of d-amphetamine or -methyl-p-tyrosine.

Two squirrel monkeys were trained on a nondiscriminated (Sidman) avoidance schedule that presented a conditional aversive stimulus (CAS) whenever the animals failed to respond within 20 sec. Shock was paired with the CAS 20% of the time. A 3 min tone followed by unavoidable shock was superimposed upon this avoidance schedule. Amphetamine (1.0, 2.0 mg/kg) increased responding without consistently affecting shock or CAS rate, while α-methyl-p-tyrosine (150, 225 mg/kg) decreased response rate and led to more CAS presentations and shocks. Withdrawal of amphetamine produced behavioral effects similar in direction but not intensity to those seen after the administration of α-methyl-p-tyrosine. Neither drug reliably altered the facilitation of avoidance response rate normally noted during the 3-min tone. These results were interpreted to reflect the role of the catecholamines in modulating the performance of an avoidance task. Furthermore, an attempt was made to speculate on the mechanism that may be responsible for the behavioral effects noted after the withdrawal of chronic amphetamine administration.

The alteration of aversive thresholds with cholinergic and adrenergic agents

Abstract Several cholinergic and adrenergic agents were administered to five squirrel monkeys in a titration schedule to ascertain their effects upon aversive thresholds. A narcotic analgesic, morphine sulfate, in several doses was able to reliably increase the aversive threshold. Scopolamine hydrobromide and d -amphetamine sulfate elevated the aversive threshold upon initial administration, but this effect was lost after the animals had experienced several drug sessions. Thus, animals demonstrated pronounced drug tolerance in response to these two agents. Amphetamine also produced increased general motor activity and stereotyped behaviors. Futhermore, amphetamine produced a response profile which strongly suggested that animals were responding without regard to the shock intensity presented. Pilocarpine nitrate and scopolamine methylbromide had no reliable effects upon behavior given alone or in conjuction with each other. α-Methyl-p-tyrosine in several doses reliably increased the aversive threshold and reduced response rates in all animals tested. These results suggested that adrenergic mechanisms may be involved in mediating the aversive qualities of electric shock.

Modulation of cholinergic activity and the aversive threshold in the rat

Abstract The analgesic potency of atropine sulfate (5.0, 10.0, 20.0, 40.0 mg/kg), eserine sulfate (0.5, 1.0, 1.5 mg/kg), pilocarpine nitrate (5.0, 10.0, 20.0 mg/kg), scopolamine methylbromide (0.5, 1.0 mg/kg) and scopolamine hydrobromide (1.0 mg/kg) was measured in the rat using the spatial preference technique. Enhanced cholinergic tone via the administration of eserine or pilocarpine in conjunction with scopolamine methylbromide produced significant increments in the aversive threshold. These increments could not be accounted for solely by changes in motor activity or the debilitating effects of enhanced peripheral cholinergic stimulation. None of the anticholinergics tested affected the aversive threshold. Scopolamine hydrobromide (1.0 mg/kg), however, was able to fully block the increments in the aversive threshold noted after the administration of pilocarpine (10.0 mg/kg). These results were interpreted to suggest that agents which enhance cholinergic tone can produce significant analgesia in the rat. While no firm conclusions can be made without further evidence, especially with regard to the antianalgesic effects of the anticholinergics, it is possible that central cholinergic mechanisms may mediate the aversive qualities of electric shock in the rat.

The effects of agents that modify muscarinic tone upon behavior controlled by an avoidance schedule that employs signaled unavoidable shock

Six male squirrel monkeys were subjected to a Sidman nondiscriminated avoidance schedule that superimposed conditioned stimuli (CS)—unavoidable shock pairings upon the ongoing avoidance behavior. Four of the six animals demonstrated facilitated avoidance response rates during the CS, while two demonstrated suppressed rates during the CS. Scopolamine hydrobromide (0.06, 0.125, 0.50, 1.0 mg/kg IM) reversed these patterns, causing the facilitators to suppress and vice versa. Scopolamine hydrobromide (0.50, 1.0 mg/kg) also led to a reliable reduction in overall response rate and an increase in the number of shocks received. Neither scopolamine methylbromide (0.50, 1.0 mg/kg), a peripheral acting anticholinergic, nor pilocarpine nitrate (1.25, 2.50 mg/kg), a muscarinic stimulant, produced any reliable effects upon avoidance behavior. These results were interpreted to indicate that the central acting antimuscarinic agent, scopolamine hydrobromide, may be able to reduce level of fear motivation either directly by interfering with cholinergic systems that mediate fear or by producing decrements in cognitive (i.e., memory) processes that are needed for animals to fully appreciate the aversive qualities of the CS.