Conditioned place preference induced by microinjection of 8-OH-DPAT into the dorsal or median raphe nucleus

Experiments were conducted to examine the ability of the selective 5-hydroxytryptamine (5-HT)1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) to induce a conditioned place preference following peripheral injection, and direct microinjection into the dorsal or median raphe nuclei. An unbiased place preference paradigm was used in which control animals showed no preference for either of two compartments differing in terms of colour (white versus black), floor texture (rough versus smooth) and olfactory cues (no odour versus acetic acid odour). Drug treatments were paired with access to either of the two compartments, and saline injections were paired with access to the other compartment. Rats experiencing a low dose of 8-OH-DPAT (125 micrograms/kg) with a specific compartment demonstrated a significant preference for that compartment over one paired with saline injections. The magnitude of this effect was similar to that observed in rats treated with 1.5 mg/kg d-amphetamine. A significant place preference was found in animals receiving injections of 8-OH-DPAT in the dorsal raphe at 0.1 microgram but not 1 microgram. Animals also displayed a preference for the compartment paired with 1 microgram 8-OH-DPAT injected into the median raphe; lower doses were not effective. These results indicate that the mechanism by which 8-OH-DPAT induces a conditioned place preference involves activation of raphe somatodendritic 5-HT1A autoreceptors, leading to a reduction in 5-HT neurotransmission. This demonstration of the rewarding properties of 8-OH-DPAT, together with previous results showing increased feeding and sexual behaviour following 8-OH-DPAT treatment, strongly suggests an important role for brain 5-HT systems in reward and reinforcement processes.