The discriminative stimulus produced by pentylenetetrazol: effects of systemic anxiolytics and anxiogenics, aggressive defeat and midazolam or muscimol infused into the amygdala

Abstract

Rats were trained to discriminate the interoceptive stimulus generated by systemic administration of pentylenetetrazol. A series of experiments confirmed earlier studies that rats generalized to the pentylenetetrazol cue following treatment with drugs purported to have anxiogenic properties, such as β-carboline carboxylic acid (βCCM) and FG 7142. The benzodiazepine antagonist, Ro 15-1788, did not generalize to the pentylenetetrazol cue. Anxiolytic drugs, such as the benzodiazepines chlordiazepoxide and midazolam, prevented discrimination of the pentylenetetrazol cue and resulted in generalization to the saline vehicle. Ritanserin, a 5-HT2 receptor antagonist and putative anxiolytic compound, did not prevent discrimination of the pentylenetetrazol cue. Subjecting the rats to aggressive defeat in a home cage intruder test (following injection of saline) resulted in a significant proportion of them generalizing to the pentylenetetrazol discriminative stimulus. This result is discussed in terms of the suggested anxiogenic nature of the effects of treatment with pentylenetetrazol. Infusion of midazolam bilaterally into the amygdala antagonized, in a dose-dependent manner, dis crimination of the interoceptive stimulus generated by systemic treatment with FG 7142 (which itself generalized to the pentylenetetrazol cue). Furthermore, infusion of the GABA agonist, muscimol, bilaterally into the amygdala antagonized the pentylenetetrazol discri minative stimulus in a dose-dependent manner. These data suggest that amygdaloid mech anisms may be involved in the generation or discrimination of the distinctive, interoceptive stimuli associated with pentylenetetrazol and the β-carboline, FG 7142. The data are discussed in the context of suggested functions of the amygdaloid complex in fear-motivated behaviour.