Blockade of presynaptic voltage-gated calcium channels in the medial prefrontal cortex of neonatal rats leads to post-pubertal alterations in locomotor behavior.
Although the etiology of neurodevelopmental mental disorders remains obscure, converging lines of evidence using animal modeling suggest a critical role for activity-dependent neurodevelopmental processes during neonatal life. Here, we report the behavioral effects of a novel technique designed to induce targeted, transient disruption of activity-dependent processes in early development via reduction of calcium-mediated neurotransmitter release. We examined the post-pubertal behavioral effects of neonatal (postnatal day 7) medial prefrontal cortex infusion of either vehicle or N-type and P/Q-type presynaptic voltage-dependent calcium channel blockers (omega-conotoxins MVIIA and MVIIC respectively; 6.8 and 45 pmol infused respectively) in rat pups. In a test of amphetamine-induced behavioral sensitization, neonatal omega-conotoxin MVIIA treatment significantly increased locomotion following repeated amphetamine injections (1.5 mg/kg i.p.) and significantly decreased locomotion following repeated saline injections relative to animals treated neonatally with vehicle. However, there was no effect of conotoxin treatment on the long-term expression of amphetamine sensitization. Neonatal treatment with omega-conotoxins had no effect on the other behaviors assayed, namely, acoustic startle response, prepulse inhibition of startle, novelty- and amphetamine-induced (1.5 mg/kg i.p.) locomotion, and anxiety-like behavior in the elevated plus-maze. These data confirm that transient, region-specific disruption of synaptic transmission during early development can have long-term effects on behaviors relevant to neurodevelopmental mental disorders.
Cassidy
Clifford M
CM
Departments of Psychiatry and Neurology and Neurosurgery, Douglas Hospital Research Centre, McGill University, 6875 LaSalle Boulevard, Verdun, Montreal, Quebec, Canada H4H 1R3.
Quirion
Rémi
R
Srivastava
Lalit K
LK
D000375:Aging / Q000502:physiology; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000378:metabolism / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism; D020865:Calcium Channels, P-Type / Q000187:drug effects / Q000378:metabolism; D000697:Central Nervous System Stimulants; D004195:Disease Models, Animal; D004347:Drug Interactions / Q000502:physiology; D001523:Mental Disorders / Q000378:metabolism / Q000503:physiopathology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013995:Time; D020960:omega-Conotoxins / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D000697:Central Nervous System Stimulants; D020960:omega-Conotoxins; C078452:ziconotide; D000661:Amphetamine