Isolation rearing enhances the locomotor stimulant properties of intra-perifornical sulpiride, but impairs the acquisition of a conditioned place preference

Abstract

Previous data indicated that infusions of the D2/D3 dopamine receptor antagonist sulpiride within the perifornical region of the lateral hypothalamus may engage neural circuitry relevant to activation of the mesoaccumbens dopamine projection. The present work examined this proposition further. Experiment 1 examined the ability of intra-perifornical sulpiride to induce a conditioned place preference, using an unbiased conditioning procedure. Thus, bilateral guide cannulae were implanted to gain access to the perifornical region of the lateral hypothalamus. Following recovery, animals were subjected to an initial exposure to the place preference apparatus. The apparatus consisted of three distinctive compartments, the central compartment allowing access to the two outermost compartments. Initial exposure indicated equal preference for each. Then, in alternating sessions, animals received infusions of sulpiride (5, 10 or 20 micrograms) before being placed in one of the two outermost compartments, and infusions of vehicle before being placed in the alternate compartment. Compartment-drug pairings were counterbalanced across animals. Four drug, and four saline sessions were completed, each being separated by at least 2 full days. On the final test day, animals were allowed free access to compartments, and the time spent in each was compared with that of initial exposure. Results showed that intra-perifornical sulpiride increased activity during drug-conditioning sessions in an incremental fashion, and supported dose-dependently the acquisition of a conditioned place preference. Experiment 2 examined the effects of isolation rearing upon the locomotor stimulant properties of intra-perifornical sulpiride, and the acquisition of a conditioned place preference. Rats were raised from weaning either alone (isolation-reared) or in groups of five (socially-reared controls) until 4 months of age. Consistent with previous reports of the effects of isolation rearing upon psychomotor stimulant responsivity, here isolates were found to be more responsive to the locomotor stimulant properties of intra-perifornical sulpiride, but were less responsive to the ability of intra-perifornical sulpiride to support the acquisition of a conditioned place preference. These data were suggested to provide further support for the proposition that blockade of dopamine receptors of the D2 family within the perifornical region of the lateral hypothalamus results in the activation of the mesoaccumbens dopamine projection, via the ventral tegmental area.

Hyperactivity to novelty induced by social isolation is not correlated with changes in D2 receptor function and binding in striatum

“…These results suggest that the in vivo activation of D2 receptors is resistant to rearing conditions and also that changes in D2 receptor function, possibly in the ventral striatum, are not involved in the enhanced increases in locomotor activity in isolated rats induced by novelty and amphetamine. The results obtained in the present study seem to be complementary to previous in vivo studies that, using a different approach (blocking instead of activating D2 receptors), have found changes in D2 sensitivity in isolated relative to grouped rats (Phillips et al 1994;Morutto and Phillips 1997;Sundstrom et al 2002) in different areas of the brain, such as nucleus accumbens (Phillips et al 1997) and lateral hypothalamus (Morutto and Phillips 1997).…”

“…For instance, at the behavioral level, a reduced sensitivity has been shown to systemic or intracerebral injections into the nucleus accumbens of D2 antagonists in isolated rats, which suggests a functional downregulation of D2 receptors in these rats (Phillips et al 1994;Sundstrom et al 2002). However, other studies have shown that the effects of intra-perifornical injections of D2 antagonists stimulating motor activity are enhanced in isolated as opposed to grouped rats (Morutto and Phillips 1997). There are no reports investigating the effects of the specific activation of D2 receptors in isolated rats.…”

Cross-sensitisation with d -amphetamine following repeated intra-perifornical sulpiride infusions

“…Recent work lends further support to this proposition. Infusions with the NMDA receptor antagonist AP5 within the ventral tegmental area, whilst showing no intrinsic e¤ect, nevertheless exhibited a potent interaction both with the locomotor stimulant properties of intra-perifornical sulpiride, and the ability of intra-perifornical sulpiride to support a conditioned placed preference (Morutto and Phillips 1997). The precise mechanisms by which intra-perifornical sulpiride leads to activation of the mesoaccumbens dopamine projection require further investigation.…”

“…Indeed, animals appear readily to self-administer sulpiride in the perifornical region, while sites either 1 mm medial or 2 mm posterior to this area do not support the acquisition of a self-administration response, weighing against signiÞcant e¤ects within regions distal to the primary site of interest (Parada et al 1995). Furthermore, recent work has shown that intra-perifornical region infusions of sulpiride dosedependently supported the acquisition of a conditioned place preference (Morutto and Phillips 1997). Thus, blockade of dopamine D 2 /D 3 receptors within the perifornical region of the lateral hypothalamus enhances a variety of behaviours associated with activity of the mesoaccumbens dopamine projection, and is accompanied by increased dopamine overßow within the nucleus accumbens.…”

Interactions between intra-perifornical region sulpiride and intra-ventral tegmental area AP5 on measures of locomotor activity and conditioned place preference

“…For example, infusions of damphetamine within the nucleus accumbens, but not in the dorsal striatum, were shown to induce a conditioned place preference (Carr and White 1983;White et al 1991). However, recent work indicated that sulpiride infusions within the perifornical area of the lateral hypothalamus also induced a robust conditioned place preference (Morutto and Phillips 1997b).…”