John R. Vogel

A simple and reliable conflict procedure for testing anti-anxiety agents.

The effects of three benzodiazepines (chlordiazepoxide, diazepam, and oxazepam), meprobamate, pentobarbital, d-amphetamine sulfate, magnesium pemoline, and scopolamine hydrobromide were studied with a simple conflict procedure in which thirsty naive rats were periodically administered shocks for licking water. The results indicated that this simple procedure clearly demonstrated “anti-anxiety” (i.e., increases in punished responding) effects with benzodiazepines, meprobamate and pentobarbital. Doses of d-amphetamine sulfate, magnesium pemoline, and scopolamine hydrobromide did not increase responding.

Cyclic Adenosine Monophosphate Phosphodiesterase in Brain: Effect on Anxiety

Drugs that reduce anxiety may be mediated by cyclic adenosine monophosphate in the brain because (i) potent anxiety-reducing drugs are also potent inhibitors of brain phosphodiesterase activity; (ii) dibutyryl cyclic adenosine monophosphate has the ability to reduce anxiety; (iii) the methylxanthines show significant anxiety-reducing effects; (iv) theophylline and chlordiazepoxide produce additive anxiety-reducing activity; and (v) there is a significant correlation between the anxiety-reducing property of drugs and their ability to inhibit phosphodiesterase activity in the brain.

Studies of the amnesic properties of scopolamine

Prior exposure to a stimulus results in a long-term loss of the effectiveness of that stimulus. Administration of scopolamine before such exposure attenuates this loss of effectiveness in animals subsequently tested without drug. These animals behave much as if they have not had prior exposure at all.

Reduction of learned taste aversions by pre-exposure to drugs.

Taste aversions are induced by a variety of psychotropic drugs. In the present experiments taste aversions induced by the barbiturate hypnotic drug, amobarbital, were dramatically reduced by prior exposure to the drug. Increasing numbers of pre-exposures were associated with larger reductions in taste aversions. Reductions in sleeping time (a widely accepted measure of tolerance to barbiturate drugs) were not correlated with reductions in taste aversions. Taste aversions induced by amobarbital were also impaired following pre-exposure to the pharmacologically dissimilar drug d-amphetamine. These results suggest that reduced taste aversions following pre-exposure to drugs may reflect habituation to drug-related stimuli and not solely the development of tolerance to those drugs.

Habituation and conditioned food aversion

Prior habituation to milk led to a marked deficit in conditioning when milk was paired with injections of atropine methylnitrate. This effect was only partially reversed with repeated conditioning trials.

Effects of chlordiazepoxide on depressed performance after reward reduction

Hungry rats were trained to lick either 4 or 32% sucrose solutions. When rats were shifted from the 32 to the 4% solution, depressed performance (relative to control groups) was observed. A single dose of chlordiazepoxide (8 mg/kg, i.p.) reversed the depression, but did not affect licking rates in control rats. When the drug was withdrawn, the depression reappeared. These data are discussed in terms of the possible effects of chlordiazepoxide on behavior that has been suppressed.

Scopolamine, atropine and conditioned fear

SummaryTwo experiments, designed to determine the effects of anticholinergics on fear-conditioning, are reported. The results indicate that scopolamine and atropine were not effective in reducing the conditioning of fear. These experiments indicate that previous findings suggestive of attenuated habituation with the antichiolnergics, cannot reasonable be accounted for in terms of a general memory deficit. Other data pertinent to this finding are discussed.

Interaction of reward magnitude and conditioned fear on the consummatory response

Three experiments are reported in which tone offset was associated with shock using a modified CER procedure. Ss were then tested for response suppression to the tone when given 4, 11.5 or 32% sucrose solution. Results indicated that there was less response suppression in the 32% Ss compared to the 4% Ss. This persisted despite wide variations in values of critical parameters.

Two-bar sucrose preference

Rats given the alternative of a high and alow concentration of sucrose on a CRF schedule gave the greatest total number of responses to the low concentration bars and made the most responses in any pair to the bar that produced the highest concentration. The introduction of an FI schedule led to an increase in the rate of responding, a shift in the maximum to a higher concentration pair, and the disappearance of preference for either bar. These results were interpreted as evidence that rate of responding and preference reflect the same underlying process.

Postconsummatory delay and goal box confinement

Four groups of rats were run in a factorial design varying goal box size (large vs small) with a 0 or 30 sec postconsummatory delay. Ss receiving postconsummatory delay during acquisition were more resistant to extinction than nondelayed Ss. As predicted, Ss delayed in the larger goal box were more resistant to extinction than those delayed in the smaller goal box.