Search

Microinjections of different doses of bicuculline methiodide (BM) were performed into the mesencephalic central gray (CG), the medial hypothalamus (MH) and lateral hypothalamus (LH). Flight reactions could be induced by microinjections of BM into either the CG or the MH. However, the type of flight behavior was different whether the injection was made in the CG or the MH. Furthermore, microinjections of 35 ng of BM in either structure produced an increase in locomotor activity whose time course differed according to the injected structure, and an increase in rearings was induced at MH but not at CG sites. At lateral hypothalamic sites, BM produced an increase in locomotor activity and rearings but no jump. These effects were antagonized in a dose-dependent manner by a local pretreatment with 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP), a GABA agonist. These results suggest that (1) at the level of both the MH and the CG, a GABAergic link is involved in the inhibition of a substrate whose activation produces aversive effects, and (2) the aversive effect induced by CG BM microinjection seems to be different from that induced by MH BM microinjection.

A place conditioning paradigm was used to examine the affective properties of FG 7142, a benzodiazepine receptor inverse agonist. At the highest dose tested (10 mg/kg, IP), FG 7142 produced a significant place aversion to the drug-paired compartment. In a second experiment, haloperidol injections were given before FG 7142. It was found that haloperidol (0.2 mg/kg) significantly reduced the measured conditioned place aversion produced by FG 7142, without exhibiting any aversive or rewarding effects by itself. These results suggest that dopamine receptors are involved in the learning or expression of conditioned place aversion induced by benzodiazepine receptor inverse agonists.

The effect of prior treatment with a GABA mimetic, SL 76002 (100 mg/kg i.p.), on amphetamine-induced locomotor activity and conditioned place preferences with amphetamine (1.5 mg/kg i.p.) was investigated. SL 76002 significantly attenuated the motor stimulant effects of amphetamine, without influencing the rewarding properties at least as determined by the place preference procedure. When injected alone, SL 76002 did not affect handling-induced locomotor activation, nor did it exhibit any aversive or reinforcing properties. The results suggest that separate neural systems may subserve the motor and rewarding properties of amphetamine.

In the rat, a microinjection of bicuculline methiodide (0.03 to 0.065 nmole) into the mesencephalic central gray (GC) provokes a flight response. At a lower dose, it reduces - or increases - the latency with which the rat switches off an electrical stimulation applied to the GC. This latency is regularly increased by a local microinjection of muscimol. These results suggest that a GABAergic link within the GC is involved in the generation of an aversive effect and of the flight response which may express it.

Alteration of GABAergic neurotransmission within the inferior colliculus (IC) appears to be involved in the generation of the audiogenic seizure (AGS) susceptibility. In the present study, we provide evidence indicating that this susceptibility may result from IC neuronal hyperexcitability to sound induced by a decreased GABAergic inhibition. In a first experiment, a unilateral microinjection of bicuculline, a GABAa antagonist, into the IC of normal rats increased the amplitude of the collicular auditory evoked potential, while the microinjection of THIP, a GABAa agonist, decreased this response. In a second experiment, a unilateral microinjection of bicuculline into the IC induced AGS susceptibility in normal rats.

This paper reviews results obtained in experiments concerning the neurochemical characteristics of the substrate involved in the control of flight reactions and the induction of aversive effects in the rat. These experiments investigated the behavioural effects produced by microinjecting into the periaqueductal grey matter (PAG) or the medial hypothalamus (MH) compounds known to interfere with the functioning of some neurotransmitter systems known to exist in these structures. The data obtained show that: the activity of the substrate involved in the production of flight reactions is tonically inhibited by the release of GABA (gamma-aminobutyric acid); the behavioural reactions produced by microinjecting GABA antagonists can be clearly distinguished, depending on whether such drugs were injected into the PAG or the MH, despite the fact that jumps were produced from either level; behavioural effects, comparable to some extent to those produced by microinjections of GABA antagonists, can be obtained by injecting drugs which act on non-GABAergic neurochemical substrates, namely opioidergic or cholinergic systems; and behavioural effects, comparable to those produced by injecting GABA antagonists into the PAG, can be obtained by injecting such drugs into various sites located in other parts of the tectum such as the inferior colliculus or adjacent structures.