The effects of clonidine on the partial reinforcement extinction effect (PREE)

Abstract

Clonidine has been reported to exert anti-anxiety effects in animals and man similar to those of benzodiazepines. The present experiment examined the effects of clonidine administration on the partial reinforcement extinction effect (PREE) which is known to be sensitive to benzodiazepine action. Two groups of rats were trained to run in a straight alley. The continuously reinforced (CRF) group received food reward on every trial. The partially reinforced (PRF) group was rewarded on a quasi-random 50% schedule. All animals were then tested in extinction. Clonidine 50 micrograms/kg was administered in a 2 X 2 design, i.e., drug-no drug in acquisition and drug-no drug in extinction. The PREE, i.e., increased resistance to extinction exhibited by PRF animals as compared to CRF animals, was obtained in animals that received saline in acquisition, independently of drug treatment in extinction, as well as in animals that received clonidine in both acquisition and extinction, but not in animals that received clonidine in acquisition alone. The administration of clonidine in extinction alone increased resistance to extinction in both the CRF and PRF animals. The increase in resistance to extinction, typically obtained with benzodiazepine treatment, indicates that clonidine exerts anxiolytic effects, supporting the involvement of the noradrenergic system in anxiety. However, clonidine did not fully reproduce the effects of benzodiazepines on the PREE, suggesting that the two classes of drugs may act via different noradrenergic mechanisms.

The signal attenuation rat model of obsessive–compulsive disorder: a review

“…Our findings suggest that the three antidepressants may facilitate extinction of lever-press responding or attenuate the extinction burst, in agreement with previous reports that acute administration of tricyclic antidepressants facilitate extinction of active avoidance and of fearinduced ultrasonic vocalization (Kikusui et al 2001;Telegdy et al 1983). Our findings seem to contradict, however, previous reports that diazepam at low doses (2-4 mg/kg), as well as other anxiolytic drugs, retards rather than facilitates the extinction of a variety of pavlovian and operant behaviors (e.g., Cowie et al 1987;Feldon and Gray 1981;Halevy et al 1986;McNaughton 1984;Soubrie et al 1978), including lever-pressing for a food reward (Thiebot et al 1983). Two findings, therefore, require an explanation: the finding that low diazepam doses decreased the number of ELP-C and ELP-U in rats undergoing regular extinction, and the finding that at these doses, diazepam had no effect on ELP-C and ELP-U in rats undergoing post-training signal attenuation.…”

Examination of reinforcement magnitude on the pharmacological disruption of fixed-ratio performance.

“…In a review of the literature, we were unable to find additional data showing differential effects of clonidine on resistance to change. Halevy, Feldon, and Weiner (1986), for example, examined clonidine's effects on rats' running speeds in a straight alleyway. Different groups of rats received food after either every trip down the alley (continuous reinforcement, CRF) or for half of the trips, on average (partial reinforcement, PRF).…”

The genetic structure of personality and learning: a phylogenetic model

“…One PREE mechanism was described by A. Amsel (1962) and occurs with trials spaced once per day for many days (Gray 1975, Rawlins et al 1985; it involves formation of conditioned signals of frustrative non-reward (Amsel 1962, Owen et al 1982, Gonzalez & Bitterman 1969, and can be blocked by a variety of drugs during acquisition that either prevent anxiety during acquisition or block REM sleep during the circadian intertrial interval (i.e., anti-anxiety, antidepressant, and stimulant drugs) (Pearlman & Becker 1974, Feldon & Weiner 1992, Halevy et al 1986, Gray 1975. It is also blocked by destruction of the dorsal noradrenergic bundle projection from the locus ceruleus to the septo-hippocampal system (Owen et al 1982) or hippocampal lesions (Rawlins et al 1985).…”