WITHDRAWAL-LIKE EFFECTS OF PENTYLENETETRAZOL AND VALPROATE IN THE NAIVE ORGANISM - A MODEL OF MOTIVATION PRODUCED BY OPIATE WITHDRAWAL

Pentylenetetrazol (PTZ) and sodium valproate (VPA) produce acutely in the naive rat various behavioural effects resembling signs of opiate w ithdrawal in the morphine-treated subject. Suggestions in the literatu re that these substances may activate directly some of the neural cons equences of opiate and drug withdrawal prompted us to look for and exa mine possible aversive effects of these substances at non-toxic doses. With a sensitive two-flavour, three-trial taste aversion procedure, r elatively low doses of PTZ and VPA (5 and 160 mg/kg, respectively) do indeed have aversive effects. The maximum aversions were produced by 1 0 and 20 mg/kg PTZ and 320 mg/kg VPA and were equivalent to those of m orphine withdrawal precipitated by 0.01-0.03 mg/kg naloxone in a morph ine pellet-implanted animal. Moreover, the maximum aversions with PTZ and VPA were significantly higher than the maximum aversions seen with naloxone in the drug-naive animal under the same training conditions. Thus, the data from the present study confirmed the notion that low d oses of PTZ and VPA in the naive animal may activate processes activat ed by drug withdrawal, including those important for the motivational effect of withdrawal. However, it was also pointed out that the lowest dose VPA producing aversion was higher than that found here to produc e writhes and ataxia (80 mg/kg) but the same as that required for shak ing (160 mg/kg), while the PTZ aversion was,at a dose lower than that known to produce a PTZ cue. Implications were discussed for using with drawal-like phenomena as a model in the non-treated organism of clinic ally-relevant withdrawal effects.