Anxiety, anxiolytics and brain stimulation reinforcement.
The premise of this review is that neuronal substrates of anxiety are amenable to investigation using brain stimulation techniques. Anxiolytics such as meprobamate and the benzodiazepines may enhance intracranial self-stimulation (ICSS) behavior. Although demonstrated by numerous investigators, this effect shows considerable variability between and within laboratories. Some of this variability is explained by sedative/muscle relaxant effects, which are dissociable from drug-induced increases in ICSS and which may mask these increases. The anticonvulsant actions of anxiolytic drugs are unlikely to account for the increases in ICSS. Rather, anxiolytics appear to increase ICSS by attenuating concurrent aversive properties of stimulation. Consistent with this explanation, anxiolytic drugs attenuate escape from aversive dorsal tegmental stimulation. The neuronal substrates of this centrally mediated escape behavior differ from those mediating footshock-induced escape. Barbiturates also enhance ICSS, possibly due in part to an excitatory component that is not involved in benzodiazepine action. Inverse benzodiazepine agonists attenuate ICSS behavior in a manner that cannot be explained by nonspecific performance impairment. These substances, however, may not necessarily enhance stimulation-induced aversiveness. A strategy is proposed to integrate brain stimulation studies with molecular approaches to anxiety. Specifically, stimulation of sites associated with fear induction or fear reduction may selectively alter the release of endogeneous anxiogens or anxiolytic substances.
Liebman
J M
JM
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000927:Anticonvulsants / Q000494:pharmacology; D001007:Anxiety / Q000503:physiopathology*; D001362:Avoidance Learning / Q000187:drug effects; D001569:Benzodiazepines; D001921:Brain / Q000502:physiology*; D001923:Brain Chemistry / Q000187:drug effects; D004558:Electric Stimulation; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects; D012054:Reinforcement, Psychology; D012653:Self Stimulation / Q000187:drug effects*
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D006993:Hypnotics and Sedatives; D009125:Muscle Relaxants, Central; D011963:Receptors, GABA-A; D001569:Benzodiazepines